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Sample records for alters extinction learning

  1. Inhibiting DNA methylation alters olfactory extinction but not acquisition learning in Apis cerana and Apis mellifera.

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    Gong, Zhiwen; Wang, Chao; Nieh, James C; Tan, Ken

    2016-07-01

    DNA methylation plays a key role in invertebrate acquisition and extinction memory. Honey bees have excellent olfactory learning, but the role of DNA methylation in memory formation has, to date, only been studied in Apis mellifera. We inhibited DNA methylation by inhibiting DNA methyltransferase (DNMT) with zebularine (zeb) and studied the resulting effects upon olfactory acquisition and extinction memory in two honey bee species, Apis cerana and A. mellifera. We used the proboscis extension reflex (PER) assay to measure memory. We provide the first demonstration that DNA methylation is also important in the olfactory extinction learning of A. cerana. DNMT did not reduce acquisition learning in either species. However, zeb bidirectionally and differentially altered extinction learning in both species. In particular, zeb provided 1h before acquisition learning improved extinction memory retention in A. mellifera, but reduced extinction memory retention in A. cerana. The reasons for these differences are unclear, but provide a basis for future studies to explore species-specific differences in the effects of methylation on memory formation.

  2. Enhancement of extinction learning attenuates ethanol-seeking behavior and alters plasticity in the prefrontal cortex.

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    Gass, Justin T; Trantham-Davidson, Heather; Kassab, Amanda S; Glen, William B; Olive, M Foster; Chandler, L Judson

    2014-05-28

    Addiction is a chronic relapsing disorder in which relapse is often initiated by exposure to drug-related cues. The present study examined the effects of mGluR5 activation on extinction of ethanol-cue-maintained responding, relapse-like behavior, and neuronal plasticity. Rats were trained to self-administer ethanol and then exposed to extinction training during which they were administered either vehicle or the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) or CDPPB. CDPPB treatment reduced active lever responding during extinction, decreased the total number of extinction sessions required to meet criteria, and attenuated cue-induced reinstatement of ethanol seeking. CDPPB facilitation of extinction was blocked by the local infusion of the mGluR5 antagonist 3-((2-methyl-4-thiazolyl)ethynyl) pyridine into the infralimbic (IfL) cortex, but had no effect when infused into the prelimbic (PrL) cortex. Analysis of dendritic spines revealed alterations in structural plasticity, whereas electrophysiological recordings demonstrated differential alterations in glutamatergic neurotransmission in the PrL and IfL cortex. Extinction was associated with increased amplitude of evoked synaptic PrL and IfL NMDA currents but reduced amplitude of PrL AMPA currents. Treatment with CDPPB prevented the extinction-induced enhancement of NMDA currents in PrL without affecting NMDA currents in the IfL. Whereas CDPPB treatment did not alter the amplitude of PrL or IfL AMPA currents, it did promote the expression of IfL calcium-permeable GluR2-lacking receptors in both abstinence- and extinction-trained rats, but had no effect in ethanol-naive rats. These results confirm changes in the PrL and IfL cortex in glutamatergic neurotransmission during extinction learning and demonstrate that manipulation of mGluR5 facilitates extinction of ethanol cues in association with neuronal plasticity.

  3. Altered consolidation of extinction-like inhibitory learning in genotype-specific dysfunctional coping fostered by chronic stress in mice.

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    Campus, P; Maiolati, M; Orsini, C; Cabib, S

    2016-12-15

    Genetic and stress-related factors interact to foster mental disorders, possibly through dysfunctional learning. In a previous study we reported that a temporary experience of reduced food availability increases forced swim (FS)-induced helplessness tested 14days after a first experience in mice of the standard inbred C57BL/6(B6) strain but reduces it in mice of the genetically unrelated DBA/2J (D2) strain. Because persistence of FS-induced helplessness influences adaptive coping with stress challenge and involve learning processes the present study tested whether the behavioral effects of restricted feeding involved altered consolidation of FS-related learning. First, we demonstrated that restricted feeding does not influence behavior expressed on the first FS experience, supporting a specific effect on persistence rather then development of helplessness. Second, we found that FS-induced c-fos expression in the infralimbic cortex (IL) was selectively enhanced in food-restricted (FR) B6 mice and reduced in FR D2 mice, supporting opposite alterations of consolidation processes involving this brain area. Third, we demonstrated that immediate post-FS inactivation of IL prevents 24h retention of acquired helplessness by continuously free-fed mice of both strains, indicating the requirement of a functioning IL for consolidation of FS-related learning in either mouse strain. Finally, in line with the known role of IL in consolidation of extinction memories, we found that restricted feeding selectively facilitated 24h retention of an acquired extinction in B6 mice whereas impairing it in D2 mice. These findings support the conclusion that an experience of reduced food availability strain-specifically affects persistence of newly acquired passive coping strategies by altering consolidation of extinction-like inhibitory learning.

  4. Trauma exposure relates to heightened stress, altered amygdala morphology and deficient extinction learning: Implications for psychopathology.

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    Cacciaglia, Raffaele; Nees, Frauke; Grimm, Oliver; Ridder, Stephanie; Pohlack, Sebastian T; Diener, Slawomira J; Liebscher, Claudia; Flor, Herta

    2017-02-01

    Stress exposure causes a structural reorganization in neurons of the amygdala. In particular, animal models have repeatedly shown that both acute and chronic stress induce neuronal hypertrophy and volumetric increase in the lateral and basolateral nuclei of amygdala. These effects are visible on the behavioral level, where stress enhances anxiety behaviors and provokes greater fear learning. We assessed stress and anxiety levels in a group of 18 healthy human trauma-exposed individuals (TR group) compared to 18 non-exposed matched controls (HC group), and related these measurements to amygdala volume. Traumas included unexpected adverse experiences such as vehicle accidents or sudden loss of a loved one. As a measure of aversive learning, we implemented a cued fear conditioning paradigm. Additionally, to provide a biological marker of chronic stress, we measured the sensitivity of the hypothalamus-pituitary-adrenal (HPA) axis using a dexamethasone suppression test. Compared to the HC, the TR group showed significantly higher levels of chronic stress, current stress and trait anxiety, as well as increased volume of the left amygdala. Specifically, we observed a focal enlargement in its lateral portion, in line with previous animal data. Compared to HC, the TR group also showed enhanced late acquisition of conditioned fear and deficient extinction learning, as well as salivary cortisol hypo-suppression to dexamethasone. Left amygdala volumes positively correlated with suppressed morning salivary cortisol. Our results indicate differences in trauma-exposed individuals which resemble those previously reported in animals exposed to stress and in patients with post-traumatic stress disorder and depression. These data provide new insights into the mechanisms through which traumatic stress might prompt vulnerability for psychopathology.

  5. Context, Learning, and Extinction

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    Gershman, Samuel J.; Blei, David M.; Niv, Yael

    2010-01-01

    A. Redish et al. (2007) proposed a reinforcement learning model of context-dependent learning and extinction in conditioning experiments, using the idea of "state classification" to categorize new observations into states. In the current article, the authors propose an interpretation of this idea in terms of normative statistical inference. They…

  6. The learning of fear extinction.

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    Furini, Cristiane; Myskiw, Jociane; Izquierdo, Ivan

    2014-11-01

    Recent work on the extinction of fear-motivated learning places emphasis on its putative circuitry and on its modulation. Extinction is the learned inhibition of retrieval of previously acquired responses. Fear extinction is used as a major component of exposure therapy in the treatment of fear memories such as those of the posttraumatic stress disorder (PTSD). It is initiated and maintained by interactions between the hippocampus, basolateral amygdala and ventromedial prefrontal cortex, which involve feedback regulation of the latter by the other two areas. Fear extinction depends on NMDA receptor activation. It is positively modulated by d-serine acting on the glycine site of NMDA receptors and blocked by AP5 (2-amino-5-phosphono propionate) in the three structures. In addition, histamine acting on H2 receptors and endocannabinoids acting on CB1 receptors in the three brain areas mentioned, and muscarinic cholinergic fibers from the medial septum to hippocampal CA1 positively modulate fear extinction. Importantly, fear extinction can be made state-dependent on circulating epinephrine, which may play a role in situations of stress. Exposure to a novel experience can strongly enhance the consolidation of fear extinction through a synaptic tagging and capture mechanism; this may be useful in the therapy of states caused by fear memory like PTSD.

  7. Fibroblast Growth Factor-2 Alters the Nature of Extinction

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    Graham, Bronwyn M.; Richardson, Rick

    2011-01-01

    These experiments examined the effects of the NMDA-receptor (NMDAr) antagonist MK801 on reacquisition and re-extinction of a conditioned fear that had been previously extinguished before injection of fibroblast growth factor-2 (FGF2) or vehicle. Recent findings have shown that relearning and re-extinction, unlike initial learning and extinction,…

  8. Adrenal-dependent diurnal modulation of conditioned fear extinction learning.

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    Woodruff, Elizabeth R; Greenwood, Benjamin N; Chun, Lauren E; Fardi, Sara; Hinds, Laura R; Spencer, Robert L

    2015-06-01

    Post traumatic stress disorder (PTSD) is associated with altered conditioned fear extinction expression and impaired circadian function including dysregulation of glucocorticoid hormone secretion. We examined in adult male rats the relationship between conditioned fear extinction learning, circadian phase, and endogenous glucocorticoids (CORT). Rats maintained on a 12h light:dark cycle were trained and tested across 3 separate daily sessions (conditioned fear acquisition and 2 extinction sessions) that were administered during either the rats' active or inactive circadian phase. In an initial experiment we found that rats at both circadian phases acquired and extinguished auditory cue conditioned fear to a similar degree in the first extinction session. However, rats trained and tested at zeitgeber time-16 (ZT16) (active phase) showed enhanced extinction memory expression during the second extinction session compared to rats trained and tested at ZT4 (inactive phase). In a follow-up experiment, adrenalectomized (ADX) or sham surgery rats were similarly trained and tested across 3 separate daily sessions at either ZT4 or ZT16. ADX had no effect on conditioned fear acquisition or conditioned fear memory. Sham ADX rats trained and tested at ZT16 exhibited better extinction learning across the two extinction sessions compared to all other groups of rats. These results indicate that conditioned fear extinction learning is modulated by time of day, and this diurnal modulation requires the presence of adrenal hormones. These results support an important role of CORT-dependent circadian processes in regulating conditioned fear extinction learning, which may be capitalized upon to optimize effective treatment of PTSD.

  9. 3,4-Methylenedioxymethamphetamine facilitates fear extinction learning.

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    Young, M B; Andero, R; Ressler, K J; Howell, L L

    2015-09-15

    Acutely administered 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') has been proposed to have long-term positive effects on post-traumatic stress disorder (PTSD) symptoms when combined with psychotherapy. No preclinical data support a mechanistic basis for these claims. Given the persistent nature of psychotherapeutic gains facilitated by MDMA, we hypothesized that MDMA improves fear extinction learning, a key process in exposure-based therapies for PTSD. In these experiments, mice were first exposed to cued fear conditioning and treated with drug vehicle or MDMA before extinction training 2 days later. MDMA was administered systemically and also directly targeted to brain structures known to contribute to extinction. In addition to behavioral measures of extinction, changes in mRNA levels of brain-derived neurotrophic factor (Bdnf) and Fos were measured after MDMA treatment and extinction. MDMA (7.8 mg kg(-1)) persistently and robustly enhanced long-term extinction when administered before extinction training. MDMA increased the expression of Fos in the amygdala and medial prefrontal cortex (mPFC), whereas increases in Bdnf expression were observed only in the amygdala after extinction training. Extinction enhancements were recapitulated when MDMA (1 μg) was infused directly into the basolateral complex of the amygdala (BLA), and enhancement was abolished when BDNF signaling was inhibited before extinction. These findings suggest that MDMA enhances fear memory extinction through a BDNF-dependent mechanism, and that MDMA may be a useful adjunct to exposure-based therapies for PTSD and other anxiety disorders characterized by altered fear learning.

  10. Extinction order and altered community structure rapidly disrupt ecosystem functioning.

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    Larsen, Trond H; Williams, Neal M; Kremen, Claire

    2005-05-01

    By causing extinctions and altering community structure, anthropogenic disturbances can disrupt processes that maintain ecosystem integrity. However, the relationship between community structure and ecosystem functioning in natural systems is poorly understood. Here we show that habitat loss appeared to disrupt ecosystem functioning by affecting extinction order, species richness and abundance. We studied pollination by bees in a mosaic of agricultural and natural habitats in California and dung burial by dung beetles on recently created islands in Venezuela. We found that large-bodied bee and beetle species tended to be both most extinction-prone and most functionally efficient, contributing to rapid functional loss. Simulations confirmed that extinction order led to greater disruption of function than predicted by random species loss. Total abundance declined with richness and also appeared to contribute to loss of function. We demonstrate conceptually and empirically how the non-random response of communities to disturbance can have unexpectedly large functional consequences.

  11. D-cycloserine facilitates context-specific fear extinction learning.

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    Bouton, Mark E; Vurbic, Drina; Woods, Amanda M

    2008-10-01

    D-cycloserine (DCS) may facilitate fear extinction learning, but the behavioral consequences and mechanisms behind this effect are not well understood at present. In this paper, we re-analyze data from previously reported null result experiments and find that rats showing above-median extinction learning during DCS treatment benefited from the drug, whereas rats showing below-median (and in this case little) extinction learning did not. Two additional experiments found that DCS facilitated extinction learning when specifically combined with a moderate, but not a small, number of extinction trials. DCS thus facilitates extinction learning only if the behavioral procedure first engages the extinction learning process. The benefits of the drug, however, were specific to the context in which extinction was learned--i.e., DCS did not prevent or influence the renewal of fear observed when the extinguished cue was tested in the original conditioning context.

  12. Slower Reacquisition after Partial Extinction in Human Contingency Learning

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    Morís, Joaquín; Barberia, Itxaso; Vadillo, Miguel A.; Andrades, Ainhoa; López, Francisco J.

    2017-01-01

    Extinction is a very relevant learning phenomenon from a theoretical and applied point of view. One of its most relevant features is that relapse phenomena often take place once the extinction training has been completed. Accordingly, as extinction-based therapies constitute the most widespread empirically validated treatment of anxiety disorders,…

  13. Rethinking Extinction.

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    Dunsmoor, Joseph E; Niv, Yael; Daw, Nathaniel; Phelps, Elizabeth A

    2015-10-07

    Extinction serves as the leading theoretical framework and experimental model to describe how learned behaviors diminish through absence of anticipated reinforcement. In the past decade, extinction has moved beyond the realm of associative learning theory and behavioral experimentation in animals and has become a topic of considerable interest in the neuroscience of learning, memory, and emotion. Here, we review research and theories of extinction, both as a learning process and as a behavioral technique, and consider whether traditional understandings warrant a re-examination. We discuss the neurobiology, cognitive factors, and major computational theories, and revisit the predominant view that extinction results in new learning that interferes with expression of the original memory. Additionally, we reconsider the limitations of extinction as a technique to prevent the relapse of maladaptive behavior and discuss novel approaches, informed by contemporary theoretical advances, that augment traditional extinction methods to target and potentially alter maladaptive memories.

  14. Extinction of Learned Fear Induces Hippocampal Place Cell Remapping.

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    Wang, Melissa E; Yuan, Robin K; Keinath, Alexander T; Ramos Álvarez, Manuel M; Muzzio, Isabel A

    2015-06-17

    The extinction of learned fear is a hippocampus-dependent process thought to embody new learning rather than erasure of the original fear memory, although it is unknown how these competing contextual memories are represented in the hippocampus. We previously demonstrated that contextual fear conditioning results in hippocampal place cell remapping and long-term stabilization of novel representations. Here we report that extinction learning also induces place cell remapping in C57BL/6 mice. Specifically, we observed cells that preferentially remapped during different stages of learning. While some cells remapped in both fear conditioning and extinction, others responded predominantly during extinction, which may serve to modify previous representations as well as encode new safe associations. Additionally, we found cells that remapped primarily during fear conditioning, which could facilitate reacquisition of the original fear association. Moreover, we also observed cells that were stable throughout learning, which may serve to encode the static aspects of the environment. The short-term remapping observed during extinction was not found in animals that did not undergo fear conditioning, or when extinction was conducted outside of the conditioning context. Finally, conditioning and extinction produced an increase in spike phase locking to the theta and gamma frequencies. However, the degree of remapping seen during conditioning and extinction only correlated with gamma synchronization. Our results suggest that the extinction learning is a complex process that involves both modification of pre-existing memories and formation of new ones, and these traces coexist within the same hippocampal representation.

  15. Differential Effects of Controllable Stress Exposure on Subsequent Extinction Learning in Adult Rats.

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    Hadad-Ophir, Osnat; Brande-Eilat, Noa; Richter-Levin, Gal

    2015-01-01

    Deficits in fear extinction are thought to be related to various anxiety disorders. While failure to extinguish conditioned fear may result in pathological anxiety levels, the ability to quickly and efficiently attenuate learned fear through extinction processes can be extremely beneficial for the individual. One of the factors that may affect the efficiency of the extinction process is prior experience of stressful situations. In the current study, we examined whether exposure to controllable stress, which is suggested to induce stress resilience, can affect subsequent fear extinction. Here, following prolonged two-way shuttle (TWS) avoidance training and a validation of acquired stress controllability, adult rats underwent either cued or contextual fear-conditioning (FC), followed by an extinction session. We further evaluated long lasting alterations of GABAergic targets in the medial pre-frontal cortex (mPFC), as these were implicated in FC and extinction and stress controllability. In cued, but not in contextual fear extinction, within-session extinction was enhanced following controllable stress compared to a control group. Interestingly, impaired extinction recall was detected in both extinction types following the stress procedure. Additionally, stress controllability-dependent alterations in GABAergic markers expression in infralimbic (IL), but not prelimbic (PL) cortex, were detected. These alterations are proposed to be related to the within-session effect, but not the recall impairment. The results emphasize the contribution of prior experience on coping with subsequent stressful experiences. Moreover, the results emphasize that exposure to controllable stress does not generally facilitate future stress coping as previously claimed, but its effects are dependent on specific features of the events taking place.

  16. Tricyclic antidepressants: effects on extinction and fear learning.

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    Ellison, G; Handel, J; Rogers, R; Weiss, J

    1975-01-01

    Rats trained to run an alley for a food reward were extinguished following injections of different antidepressants. When retested several days later, the animals extinguished following pretreatment with the NE reuptake blocker protriptyline showed faster running speeds than did the other groups. Other rats given electrical shocks following pretreatment with protriptyline avoided the compartment in which they had been shocked less than did animals shocked following pretreatment with other antidepressants. This implies an interferance with some aspect of the learning or consolidation process which is correlated with the degree of NE reuptake blockage. It is hypothesized that NE terminals are deactivated following frustrative nonreward or punishment by the conversion and reuptake of the released NE to an altered extinction molecule.

  17. Hippocampus NMDA receptors selectively mediate latent extinction of place learning.

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    Goodman, Jarid; Gabriele, Amanda; Packard, Mark G

    2016-09-01

    Extinction of maze learning may be achieved with or without the animal performing the previously acquired response. In typical "response extinction," animals are given the opportunity to make the previously acquired approach response toward the goal location of the maze without reinforcement. In "latent extinction," animals are not given the opportunity to make the previously acquired response and instead are confined to the previous goal location without reinforcement. Previous evidence indicates that the effectiveness of these protocols may depend on the type of memory being extinguished. Thus, one aim of the present study was to further examine the effectiveness of response and latent extinction protocols across dorsolateral striatum (DLS)-dependent response learning and hippocampus-dependent place learning tasks. In addition, previous neural inactivation experiments indicate a selective role for the hippocampus in latent extinction, but have not investigated the precise neurotransmitter mechanisms involved. Thus, the present study also examined whether latent extinction of place learning might depend on NMDA receptor activity in the hippocampus. In experiment 1, adult male Long-Evans rats were trained in a response learning task in a water plus-maze, in which animals were reinforced to make a consistent body-turn response to reach an invisible escape platform. Results indicated that response extinction, but not latent extinction, was effective at extinguishing memory in the response learning task. In experiment 2, rats were trained in a place learning task, in which animals were reinforced to approach a consistent spatial location containing the hidden escape platform. In experiment 2, animals also received intra-hippocampal infusions of the NMDA receptor antagonist 2-amino-5-phosphopentanoic acid (AP5; 5.0 or 7.5 ug/0.5 µg) or saline vehicle immediately before response or latent extinction training. Results indicated that both extinction protocols were

  18. Sensory cortical population dynamics uniquely track behavior across learning and extinction.

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    Moran, Anan; Katz, Donald B

    2014-01-22

    Neural responses in many cortical regions encode information relevant to behavior: information that necessarily changes as that behavior changes with learning. Although such responses are reasonably theorized to be related to behavior causation, the true nature of that relationship cannot be clarified by simple learning studies, which show primarily that responses change with experience. Neural activity that truly tracks behavior (as opposed to simply changing with experience) will not only change with learning but also change back when that learning is extinguished. Here, we directly probed for this pattern, recording the activity of ensembles of gustatory cortical single neurons as rats that normally consumed sucrose avidly were trained first to reject it (i.e., conditioned taste aversion learning) and then to enjoy it again (i.e., extinction), all within 49 h. Both learning and extinction altered cortical responses, consistent with the suggestion (based on indirect evidence) that extinction is a novel form of learning. But despite the fact that, as expected, postextinction single-neuron responses did not resemble "naive responses," ensemble response dynamics changed with learning and reverted with extinction: both the speed of stimulus processing and the relationships among ensemble responses to the different stimuli tracked behavioral relevance. These data suggest that population coding is linked to behavior with a fidelity that single-neuron coding is not.

  19. Behavioral and neural bases of extinction learning in Hermissenda

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    Joel S. Cavallo

    2014-08-01

    Full Text Available Extinction of classical conditioning is thought to produce new learning that masks or interferes with the original memory. However, research in the nudibranch Hermissenda crassicornis (H.c. has challenged this view, and instead suggested that extinction erased the original associative memory. We have re-examined extinction in H.c. to test whether extinguished associative memories can be detected on the behavioral and cellular levels, and to characterize the temporal variables involved. Associative conditioning using pairings of light (CS and rotation (US produced characteristic suppression of H.c. phototactic behavior. A single session of extinction training (repeated light-alone presentations reversed suppressed behavior back to pre-training levels when administered 15 min after associative conditioning. This effect was abolished if extinction was delayed by 23 hr, and yet was recovered using extended extinction training (three consecutive daily extinction sessions. Extinguished phototactic suppression did not spontaneously recover at any retention interval tested (2-, 24-, 48-, 72-hr, or after additional US presentations (no observed reinstatement. Extinction training (single session, 15 min interval also reversed the pairing-produced increases in light-evoked spike frequencies of Type B photoreceptors, an identified site of associative memory storage that is causally related to phototactic suppression. These results suggest that the behavioral effects of extinction training are not due to temporary suppression of associative memories, but instead represent a reversal of the underlying cellular changes necessary for the expression of learning. In the companion article, we further elucidate mechanisms responsible for extinction-produced reversal of memory-related neural plasticity in Type B photoreceptors.

  20. Extinction learning, reconsolidation and the internal reinforcement hypothesis.

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    Eisenhardt, Dorothea; Menzel, Randolf

    2007-02-01

    Retrieving a consolidated memory--by exposing an animal to the learned stimulus but not to the associated reinforcement--leads to two opposing processes: one that weakens the old memory as a result of extinction learning, and another that strengthens the old, already-consolidated memory as a result of some less well-understood form of learning. This latter process of memory strengthening is often referred to as "reconsolidation", since protein synthesis can inhibit this form of memory formation. Although the behavioral phenomena of the two antagonizing forms of learning are well documented, the mechanisms behind the corresponding processes of memory formation are still quite controversial. Referring to results of extinction/reconsolidation experiments in honeybees, we argue that two opposing learning processes--with their respective consolidation phases and memories--are initiated by retrieval trials: extinction learning and reminder learning, the latter leading to the phenomenon of spontaneous recovery from extinction, a process that can be blocked with protein synthesis inhibition.

  1. Altered primary production during mass-extinction events

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    van de Schootbrugge, B.; Gollner, S.

    2013-01-01

    The Big Five mass-extinction events are characterized by dramatic changes in primary producers. Initial disturbance to primary producers is usually followed by a succession of pioneers that represent qualitative and quantitative changes in standing crops of land plants and/or phytoplankton. On land,

  2. D-cycloserine deters reacquisition of cocaine self-administration by augmenting extinction learning.

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    Nic Dhonnchadha, Bríd A; Szalay, Jonathan J; Achat-Mendes, Cindy; Platt, Donna M; Otto, Michael W; Spealman, Roger D; Kantak, Kathleen M

    2010-01-01

    Augmentation of cue exposure (extinction) therapy with cognitive-enhancing pharmacotherapy may offer an effective strategy to combat cocaine relapse. To investigate this possibility at the preclinical level, rats and squirrel monkeys were trained to self-administer cocaine paired with a brief visual cue. Lever pressing was subsequently extinguished by withholding cocaine injections while maintaining response-contingent presentations of the cue. The glycine partial agonist D-cycloserine (DCS; 15 and 30 mg/kg in rats, 3 and 10 mg/kg in monkeys) was evaluated for its effects on the rate of extinction and subsequent reacquisition of cocaine self-administration. Compared with vehicle, pretreatment with 30 mg/kg DCS 0.5 h before extinction training reduced the number of responses and latency to reach the extinction criterion in rats, but neither dose of DCS altered these measures in monkeys. In both species, pretreatment with the higher dose of DCS before extinction training significantly attenuated reacquisition of cocaine self-administration compared with either extinction training in the absence of DCS or DCS in the absence of explicit extinction. Furthermore, treatment with 30 mg/kg DCS accompanied by brief handling (a stress induction) immediately after but not 6 h after extinction training attenuated reacquisition of cocaine self-administration in rats. No adverse effects of 10 mg/kg DCS were evident in quantitative observational studies in monkeys. The results suggest that DCS augmented consolidation of extinction learning to deter reacquisition of cocaine self-administration in rats and monkeys. The results suggest that DCS combined with exposure therapy may constitute a rational strategy for the clinical management of cocaine relapse.

  3. Reconciling Reinforcement Learning Models with Behavioral Extinction and Renewal: Implications for Addiction, Relapse, and Problem Gambling

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    Redish, A. David; Jensen, Steve; Johnson, Adam; Kurth-Nelson, Zeb

    2007-01-01

    Because learned associations are quickly renewed following extinction, the extinction process must include processes other than unlearning. However, reinforcement learning models, such as the temporal difference reinforcement learning (TDRL) model, treat extinction as an unlearning of associated value and are thus unable to capture renewal. TDRL…

  4. The Effect of D-Cycloserine on Immediate vs. Delayed Extinction of Learned Fear

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    Langton, Julia M.; Richardson, Rick

    2010-01-01

    We compared the effect of D-cycloserine (DCS) on immediate (10 min after conditioning) and delayed (24 h after conditioning) extinction of learned fear in rats. DCS facilitated both immediate and delayed extinction when the drug was administered after extinction training. However, DCS did not facilitate immediate extinction when administered prior…

  5. Mild traumatic brain injury with social defeat stress alters anxiety, contextual fear extinction, and limbic monoamines in adult rats

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    Daniel eDavies

    2016-04-01

    Full Text Available Mild traumatic brain injury (mTBI produces symptoms similar to those typifying posttraumatic stress disorder (PTSD in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mTBI induction, and 6 days later were tested either for anxiety-like behavior using the elevated plus maze (EPM, or for contextual fear conditioning and extinction. Brains were collected 24 hr after EPM testing, and tissue from various limbic regions analyzed for content of monoamines, their precursors and metabolites using HPLC with electrochemical detection. Either social defeat or mTBI alone decreased time spent in open arms of the EPM, indicating greater anxiety-like behavior. However, this effect was enhanced by the combination of treatments. Further, rats exposed to both social defeat and mTBI exhibited greater freezing within extinction sessions compared to all other groups, suggesting impaired contextual fear extinction. Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning. The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes.

  6. Nothing is safe: Intolerance of uncertainty is associated with compromised fear extinction learning.

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    Morriss, Jayne; Christakou, Anastasia; van Reekum, Carien M

    2016-12-01

    Extinction-resistant fear is considered to be a central feature of pathological anxiety. Here we sought to determine if individual differences in Intolerance of Uncertainty (IU), a potential risk factor for anxiety disorders, underlies compromised fear extinction. We tested this hypothesis by recording electrodermal activity in 38 healthy participants during fear acquisition and extinction. We assessed the temporality of fear extinction, by examining early and late extinction learning. During early extinction, low IU was associated with larger skin conductance responses to learned threat vs. safety cues, whereas high IU was associated with skin conductance responding to both threat and safety cues, but no cue discrimination. During late extinction, low IU showed no difference in skin conductance between learned threat and safety cues, whilst high IU predicted continued fear expression to learned threat, indexed by larger skin conductance to threat vs. safety cues. These findings suggest a critical role of uncertainty-based mechanisms in the maintenance of learned fear.

  7. Vagus Nerve Stimulation Reduces Cocaine Seeking and Alters Plasticity in the Extinction Network

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    Childs, Jessica E.; DeLeon, Jaime; Nickel, Emily; Kroener, Sven

    2017-01-01

    Drugs of abuse cause changes in the prefrontal cortex (PFC) and associated regions that impair inhibitory control over drug-seeking. Breaking the contingencies between drug-associated cues and the delivery of the reward during extinction learning reduces rates of relapse. Here we used vagus nerve stimulation (VNS) to induce targeted synaptic…

  8. Noradrenergic stimulation modulates activation of extinction-related brain regions and enhances contextual extinction learning without affecting renewal

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    Silke eLissek

    2015-02-01

    Full Text Available Renewal in extinction learning describes the recovery of an extinguished response if the extinction context differs from the context present during acquisition and recall. Attention may have a role in contextual modulation of behavior and contribute to the renewal effect, while noradrenaline is involved in attentional processing. In this functional magnetic resonance imaging (fMRI study we investigated the role of the noradrenergic system for behavioral and brain activation correlates of contextual extinction and renewal, with a particular focus upon hippocampus and ventromedial PFC, which have crucial roles in processing of renewal. Healthy human volunteers received a single dose of the NA reuptake inhibitor atomoxetine prior to extinction learning. During extinction of previously acquired cue-outcome associations, cues were presented in a novel context (ABA or in the acquisition context (AAA. In recall, all cues were again presented in the acquisition context. Atomoxetine participants (ATO showed significantly faster extinction compared to placebo (PLAC. However, atomoxetine did not affect renewal. Hippocampal activation was higher in ATO during extinction and recall, as was ventromedial PFC activation, except for ABA recall. Moreover, ATO showed stronger recruitment of insula, anterior cingulate, and dorsolateral/orbitofrontal PFC. Across groups, cingulate, hippocampus and vmPFC activity during ABA extinction correlated with recall performance, suggesting high relevance of these regions for processing the renewal effect. In summary, the noradrenergic system appears to be involved in the modification of established associations during extinction learning and thus has a role in behavioral flexibility. The assignment of an association to a context and the subsequent decision on an adequate response, however, presumably operate largely independently of noradrenergic mechanisms.

  9. Stress-enhanced fear learning in rats is resistant to the effects of immediate massed extinction.

    Science.gov (United States)

    Long, Virginia A; Fanselow, Michael S

    2012-11-01

    Enhanced fear learning occurs subsequent to traumatic or stressful events and is a persistent challenge to the treatment of post-traumatic stress disorder (PTSD). Facilitation of learning produced by prior stress can elicit an exaggerated fear response to a minimally aversive event or stimulus. Stress-enhanced fear learning (SEFL) is a rat model of PTSD; rats previously exposed to the SEFL 15 electrical shocks procedure exhibit several behavioral responses similar to those seen in patients with PTSD. However, past reports found that SEFL is not mitigated by extinction (a model of exposure therapy) when the spaced extinction began 24 h after stress. Recent studies found that extinction from 10 min to 1 h subsequent to fear conditioning "erased" learning, whereas later extinction, occurring from 24 to 72 h after conditioning did not. Other studies indicate that massed extinction is more effective than spaced procedures. Therefore, we examined the time-dependent nature of extinction on the stress-induced enhancement of fear learning using a massed trial's procedure. Experimental rats received 15 foot shocks and were given either no extinction or massed extinction 10 min or 72 h later. Our present data indicate that SEFL, following traumatic stress, is resistant to immediate massed extinction. Experimental rats showed exaggerated new fear learning regardless of when extinction training occurred. Thus, post-traumatic reactivity such as SEFL does not seem responsive to extinction treatments.

  10. Forming Competing Fear Learning and Extinction Memories in Adolescence Makes Fear Difficult to Inhibit

    Science.gov (United States)

    Baker, Kathryn D.; Richardson, Rick

    2015-01-01

    Fear inhibition is markedly impaired in adolescent rodents and humans. The present experiments investigated whether this impairment is critically determined by the animal's age at the time of fear learning or their age at fear extinction. Male rats (n = 170) were tested for extinction retention after conditioning and extinction at different ages.…

  11. Forming competing fear learning and extinction memories in adolescence makes fear difficult to inhibit

    OpenAIRE

    Baker, Kathryn D.; Richardson, Rick

    2015-01-01

    Fear inhibition is markedly impaired in adolescent rodents and humans. The present experiments investigated whether this impairment is critically determined by the animal's age at the time of fear learning or their age at fear extinction. Male rats (n = 170) were tested for extinction retention after conditioning and extinction at different ages. We examined neural correlates of impaired extinction retention by detection of phosphorylated mitogen-activated protein kinase immunoreactivity (pMA...

  12. Compound Stimulus Presentation Does Not Deepen Extinction in Human Causal Learning

    Science.gov (United States)

    Griffiths, Oren; Holmes, Nathan; Westbrook, R. Fred

    2017-01-01

    Models of associative learning have proposed that cue-outcome learning critically depends on the degree of prediction error encountered during training. Two experiments examined the role of error-driven extinction learning in a human causal learning task. Target cues underwent extinction in the presence of additional cues, which differed in the degree to which they predicted the outcome, thereby manipulating outcome expectancy and, in the absence of any change in reinforcement, prediction error. These prediction error manipulations have each been shown to modulate extinction learning in aversive conditioning studies. While both manipulations resulted in increased prediction error during training, neither enhanced extinction in the present human learning task (one manipulation resulted in less extinction at test). The results are discussed with reference to the types of associations that are regulated by prediction error, the types of error terms involved in their regulation, and how these interact with parameters involved in training. PMID:28232809

  13. Cannabinoid modulation of prefrontal-limbic activation during fear extinction learning and recall in humans.

    Science.gov (United States)

    Rabinak, Christine A; Angstadt, Mike; Lyons, Maryssa; Mori, Shoko; Milad, Mohammed R; Liberzon, Israel; Phan, K Luan

    2014-09-01

    Pre-extinction administration of Δ9-tetrahydrocannibinol (THC) facilitates recall of extinction in healthy humans, and evidence from animal studies suggest that this likely occurs via enhancement of the cannabinoid system within the ventromedial prefrontal cortex (vmPFC) and hippocampus (HIPP), brain structures critical to fear extinction. However, the effect of cannabinoids on the underlying neural circuitry of extinction memory recall in humans has not been demonstrated. We conducted a functional magnetic resonance imaging (fMRI) study using a randomized, double-blind, placebo-controlled, between-subjects design (N=14/group) coupled with a standard Pavlovian fear extinction paradigm and an acute pharmacological challenge with oral dronabinol (synthetic THC) in healthy adult volunteers. We examined the effects of THC on vmPFC and HIPP activation when tested for recall of extinction learning 24 h after extinction learning. Compared to subjects who received placebo, participants who received THC showed increased vmPFC and HIPP activation to a previously extinguished conditioned stimulus (CS+E) during extinction memory recall. This study provides the first evidence that pre-extinction administration of THC modulates prefrontal-limbic circuits during fear extinction in humans and prompts future investigation to test if cannabinoid agonists can rescue or correct the impaired behavioral and neural function during extinction recall in patients with PTSD. Ultimately, the cannabinoid system may serve as a promising target for innovative intervention strategies (e.g. pharmacological enhancement of exposure-based therapy) in PTSD and other fear learning-related disorders.

  14. Transient inactivation of the pigeon hippocampus or the nidopallium caudolaterale during extinction learning impairs extinction retrieval in an appetitive conditioning paradigm.

    Science.gov (United States)

    Lengersdorf, Daniel; Stüttgen, Maik C; Uengoer, Metin; Güntürkün, Onur

    2014-05-15

    The majority of experiments exploring context-dependent extinction learning employ Pavlovian fear conditioning in rodents. Since mechanisms of appetitive and aversive learning are known to differ at the neuronal level, we sought to investigate extinction learning in an appetitive setting. Working with pigeons, we established a within-subject ABA renewal paradigm based on Rescorla (Q J Exp Psychol 61:1793) and combined it with pharmacological interventions during extinction. From the fear conditioning literature, it is known that both prefrontal cortex and the hippocampus are core structures for context-specific extinction learning. Accordingly, we transiently inactivated the nidopallium caudolaterale (NCL, a functional analogue of mammalian prefrontal cortex) and the hippocampus in separate experiments by intracranial infusion of the sodium-channel blocker tetrodotoxin immediately before extinction training. We find that TTX in both structures non-specifically suppresses conditioned responding, as revealed by a reduction of response rate to both the extinguished conditioned stimulus and a control stimulus which remained reinforced throughout the experiment. Furthermore, TTX during extinction training impaired later extinction retrieval assessed under drug-free conditions. This was true when responding to the extinguished stimulus was assessed in the context of extinction but not when tested in the context of acquisition, although both contexts were matched with respect to their history of conditioning. These results indicate that both NCL and hippocampus are involved in extinction learning under appetitive conditions or, more specifically, in the consolidation of extinction memory, and that their contribution to extinction is context-specific.

  15. Impaired fear extinction learning and cortico-amygdala circuit abnormalities in a common genetic mouse strain

    OpenAIRE

    Hefner, Kathryn; Whittle, Nigel; Juhasz, Jaynann; Norcross, Maxine; Karlsson, Rose-Marie; Saksida, Lisa M.; Bussey, Timothy J.; Singewald, Nicolas; Holmes, Andrew

    2008-01-01

    Fear extinction is a form of new learning that results in the inhibition of conditioned fear. Trait deficits in fear extinction are a risk factor for anxiety disorders. There are few examples of naturally-occurring animal models of impaired extinction. The present study compared fear extinction in a panel of inbred mouse strains. This strain survey revealed an impairment in fear extinction in 129/SvImJ (129S1). The phenotypic specificity of this deficit was evaluated by comparing 129S1 and C5...

  16. A Role of Protein Degradation in Memory Consolidation after Initial Learning and Extinction Learning in the Honeybee ("Apis mellifera")

    Science.gov (United States)

    Felsenberg, Johannes; Dombrowski, Vincent; Eisenhardt, Dorothea

    2012-01-01

    Protein degradation is known to affect memory formation after extinction learning. We demonstrate here that an inhibitor of protein degradation, MG132, interferes with memory formation after extinction learning in a classical appetitive conditioning paradigm. In addition, we find an enhancement of memory formation when the same inhibitor is…

  17. Pre-trauma individual differences in extinction learning predict posttraumatic stress.

    Science.gov (United States)

    Lommen, Miriam J J; Engelhard, Iris M; Sijbrandij, Marit; van den Hout, Marcel A; Hermans, Dirk

    2013-02-01

    In the aftermath of a traumatic event, many people suffer from psychological distress, but only a minority develops posttraumatic stress disorder (PTSD). Pre-trauma individual differences in fear conditioning, most notably reduced extinction learning, have been proposed as playing an important role in the etiology of PTSD. However, prospective data are lacking. In this study, we prospectively tested whether reduced extinction was a predictor for later posttraumatic stress. Dutch soldiers (N = 249) were administered a conditioning task before their four-month deployment to Afghanistan to asses individual differences in extinction learning. After returning home, posttraumatic stress was measured. Results showed that reduced extinction learning before deployment predicted subsequent PTSD symptom severity, over and beyond degree of pre-deployment stress symptoms, neuroticism, and exposure to stressors on deployment. The findings suggest that reduced extinction learning may play a role in the development of PTSD.

  18. mGlu5 Receptors and Relapse to Cocaine-Seeking: The Role of Receptor Trafficking in Postrelapse Extinction Learning Deficits

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    Lori A. Knackstedt

    2016-01-01

    Full Text Available We have previously demonstrated that MTEP, an allosteric antagonist of mGlu5, infused into the nucleus accumbens attenuates relapse after abstinence from cocaine self-administration. MTEP infused into the dorsolateral striatum (dlSTR does not alter relapse but has long-lasting effects on subsequent extinction learning. Here we tested whether systemic MTEP would prevent relapse after abstinence or alter extinction learning. We also investigated the mechanism of action by which intra-dlSTR MTEP on test day alters extinction on subsequent days. Animals self-administered cocaine for 12 days followed by abstinence for 20-21 days. MTEP (0.5–5 mg/kg IP was administered prior to placement into the operant chamber for a context-primed relapse test. A separate group of animals received intra-dlSTR MTEP prior to the relapse test and were sacrificed day later. Systemic administration of MTEP attenuated abstinent-relapse without significantly affecting extinction learning. Surface biotinylation analysis of protein expression in the dlSTR revealed that, in cocaine animals, intra-dlSTR MTEP administration decreased mGlu5 surface expression and prevented changes in Arc and GluA1/GluA2 observed in their vehicle counterparts. Thus, blockade of mGlu5 receptors may be utilized in future treatment strategies for relapse prevention in humans, although the effects of chronic blockade on extinction learning should be further evaluated.

  19. Adrenergic drugs modify the level of noradrenaline in the insular cortex and alter extinction of conditioned taste aversion in rats.

    Science.gov (United States)

    Fresquet, Nadine; Angst, Marie-Josée; Schleef, Carmen; Gobaille, Serge; Sandner, Guy

    2007-03-12

    We compared the effect of conditioned taste aversion in rats by measuring the amount of sucrose that they drunk after conditioning, which differed according to whether rats had drunk the sucrose freely (SD: self drinking) during the conditioning session, or had been forced to drink it (IO: intra-oral administration through a chronically implanted cannula). The SD procedure delayed the extinction of conditioned taste aversion. Enhanced arousal, alertness, awareness or attention in the SD condition may have strengthened the memory of the taste. Brain noradrenergic networks are involved in such processes. We administered two noradrenergic drugs that produce opposite effects on noradrenaline release in the brain, methoxy-idazoxan, RX821002 (1mg/kg, i.p.), and guanfacine (0.12mg/kg, i.p.). We evaluated their effect (i) on the level of noradrenaline in the gustatory cortex using microdialysis, (ii) on glycaemia that is an essential factor of taste learning and (iii) on the comparative SD versus IO conditioned taste aversion protocol mentioned above. Injecting RX821001 increased the level of noradrenaline in the gustatory cortex up to two-fold of the baseline. This effect lasted 1h. The same dose of RX821002 did not elicit any alteration of glycaemia. It enhanced extinction of conditioned taste aversion in the SD group of rats. Injecting 0.12mg/kg of guanfacine produced the opposite effect. The noradrenaline level of the gustatory cortex decreased, but only down to 20% of the baseline. This decrease lasted 2h. Guanfacine increased glycaemia. Extinction of conditioned taste aversion was only marginally decreased by guanfacine in the SD group of rats. These results fit with Aston-Jones' point of view that the role of the noradrenergic coeruleo-cortical system may be to enhance arousal, alertness, awareness or attention to an event by a transient increase of cortical noradrenaline.

  20. Cortisol modifies extinction learning of recently acquired fear in men.

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    Merz, Christian Josef; Hermann, Andrea; Stark, Rudolf; Wolf, Oliver Tobias

    2014-09-01

    Exposure therapy builds on the mechanism of fear extinction leading to decreased fear responses. How the stress hormone cortisol affects brain regions involved in fear extinction in humans is unknown. For this reason, we tested 32 men randomly assigned to receive either 30 mg hydrocortisone or placebo 45 min before fear extinction. In fear acquisition, a picture of a geometrical figure was either partially paired (conditioned stimulus; CS+) or not paired (CS-) with an electrical stimulation (unconditioned stimulus; UCS). In fear extinction, each CS was presented again, but no UCS occurred. Cortisol increased conditioned skin conductance responses in early and late extinction. In early extinction, higher activation towards the CS- than to the CS+ was found in the amygdala, hippocampus and posterior parahippocampal gyrus. This pattern might be associated with the establishment of a new memory trace. In late extinction, the placebo compared with the cortisol group displayed enhanced CS+/CS- differentiation in the amygdala, medial frontal cortex and nucleus accumbens. A change from early deactivation to late activation of the extinction circuit as seen in the placebo group seems to be needed to enhance extinction and to reduce fear. Cortisol appears to interfere with this process thereby impairing extinction of recently acquired conditioned fear.

  1. Cued reacquisition trials during extinction weaken contextual renewal in human predictive learning

    NARCIS (Netherlands)

    Effting, M.; Vervliet, B.; Beckers, T.; Kindt, M.

    2013-01-01

    Extinction is generally more context specific than acquisition, as illustrated by the renewal effect. While most strategies to counteract renewal focus on decreasing the context specificity of extinction, the present work aimed at increasing the context specificity of acquisition learning. Two exper

  2. Extinction as New Learning versus Unlearning: Considerations from a Computer Simulation of the Cerebellum

    Science.gov (United States)

    Mauk, Michael D.; Ohyama, Tatsuya

    2004-01-01

    Like many forms of Pavlovian conditioning, eyelid conditioning displays robust extinction. We used a computer simulation of the cerebellum as a tool to consider the widely accepted view that extinction involves new, inhibitory learning rather than unlearning of acquisition. Previously, this simulation suggested basic mechanistic features of…

  3. Cued Reacquisition Trials during Extinction Weaken Contextual Renewal in Human Predictive Learning

    Science.gov (United States)

    Effting, Marieke; Vervliet, Bram; Beckers, Tom; Kindt, Merel

    2013-01-01

    Extinction is generally more context specific than acquisition, as illustrated by the renewal effect. While most strategies to counteract renewal focus on decreasing the context specificity of extinction, the present work aimed at increasing the context specificity of acquisition learning. Two experiments examined whether presenting cued…

  4. Blockade of Dopamine Activity in the Nucleus Accumbens Impairs Learning Extinction of Conditioned Fear

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    Holtzman-Assif, Orit; Laurent, Vincent; Westbrook, R. Frederick

    2010-01-01

    Three experiments used rats to investigate the role of dopamine activity in learning to inhibit conditioned fear responses (freezing) in extinction. In Experiment 1, rats systemically injected with the D2 dopamine antagonist, haloperidol, froze more across multiple extinction sessions and on a drug-free retention test than control rats. In…

  5. Stress enhances the consolidation of extinction memory in a predictive learning task

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    Tanja eHamacher-Dang

    2013-08-01

    Full Text Available Extinction is not always permanent, as indicated by several types of recovery effects, such as the renewal effect, which may occur after a context change and points towards the importance of contextual cues. Strengthening the retrieval of extinction memory is a crucial aim of extinction-based psychotherapeutic treatments of anxiety disorders to prevent relapse. Stress is known to modulate learning and memory, with mostly enhancing effects on memory consolidation. However, whether such a consolidation-enhancing effect of acute stress can also be found for extinction memory has not yet been examined in humans. In this study, we investigated the effect of stress after extinction learning on the retrieval of extinction memory in a predictive learning renewal paradigm. Participants took the part of being the doctor of a fictitious patient and learned to predict whether certain food stimuli were associated with ‘stomach trouble’ in two different restaurants (contexts. On the first day, critical stimuli were associated with stomach trouble in context A (acquisition phase. On the second day, these associations were extinguished in context B. Directly after extinction, participants were either exposed to a stressor (socially evaluated cold pressor test; n = 22 or a control condition (n = 24. On the third day, we tested retrieval of critical associations in contexts A and B. Participants exposed to stress after extinction exhibited a reduced recovery of responding at test in context B, suggesting that stress may context-dependently enhance the consolidation of extinction memory. Furthermore, the increase in cortisol in response to the stressor was negatively correlated with the recovery of responding in context A. Our findings suggest that in parallel to the known effects of stress on the consolidation of episodic memory, stress also enhances the consolidation of extinction memory, which might be relevant for potential applications in extinction

  6. Learning and memory in conditioned fear extinction: effects of D-cycloserine.

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    Vervliet, Bram

    2008-03-01

    This review addresses the effects of the cognitive enhancer D-cycloserine (DCS) on the memory processes that occur in conditioned fear extinction, which is the experimental model for exposure techniques to reduce clinical anxiety. All reported rat studies show an enhanced fear extinction effect when DCS is administered acutely before or shortly after extinction training. DCS also promotes the generalization of this fear extinction effect. In addition, DCS reduces some forms of relapse (reduced reinstatement, reduced spontaneous recovery), but not others (contextual renewal, rapid reacquisition). It is argued that this pattern of results is best explained by assuming that DCS promotes extinction learning to the background context, resulting in enhanced contextual inhibition. Four human studies have produced mixed results, but some methodological issues complicate the reported failures. It is concluded that DCS is a promising tool as an adjunct to extinction techniques in exposure treatment, but that more pre-clinical and clinical research is needed to fully characterize its behavioral consequences.

  7. Rethinking Extinction

    OpenAIRE

    Dunsmoor, Joseph E.; Niv, Yael; Daw, Nathaniel; Phelps, Elizabeth A.

    2015-01-01

    Extinction serves as the leading theoretical framework and experimental model to describe how learned behaviors diminish through absence of anticipated reinforcement. In the past decade, extinction has moved beyond the realm of associative learning theory and behavioral experimentation in animals and has become a topic of considerable interest in the neuroscience of learning, memory, and emotion. Here, we review research and theories of extinction, both as a learning process and as a behavior...

  8. Impaired contextual fear extinction learning is associated with aberrant regulation of CHD-type chromatin remodeling factors

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    Alexandra eWille

    2015-11-01

    Full Text Available Successful attenuation of fearful memories is a cognitive process requiring initiation of highly coordinated transcription programs. Chromatin-modulating mechanisms such as DNA methylation and histone modifications, including acetylation, are key regulators of these processes. However, knowledge concerning the role of ATP-dependent chromatin remodeling factors (ChRFs being required for successful fear extinction is lacking. Underscoring the potential importance of these factors that alter histone-DNA contacts within nucleosomes are recent genome-wide association studies linking several ChRFs to various human cognitive and psychiatric disorders. To better understand the role of ChRFs in the brain, and since to date little is known about ChRF expression in the brain, we performed a comprehensive survey of expression levels of 24 ATP-dependent remodelers across different brain areas, and we identified several distinct high molecular weight complexes by chromatographic methods. We next aimed to gain novel insight into the potential regulation of ChRFs in different brain regions in association with normal and impaired fear extinction learning. To this end, we established the 129S1/SvImJ (S1 laboratory mouse strain as a model for compromised contextual fear extinction learning that can be rescued by dietary zinc restriction. Using this model along with genetically related but fear extinction-competent 129S6/SvEv (S6 mice as controls, we found that impaired fear extinction in S1 was associated with enhanced ventral hippocampal expression of CHD1 and reduced expression of CHD5 that was normalized following successful rescue of impaired fear extinction. Moreover, a select reduction in CHD3 expression was observed in the ventral hippocampus following successful rescue of fear extinction in S1 mice. Taken together, these data provide novel insight into the regulation of specific ChRFs following an impaired cognitive process and its rescue, and they suggest

  9. Extinction learning is slower, weaker and less context specific after alcohol.

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    Bisby, James A; King, John A; Sulpizio, Valentina; Degeilh, Fanny; Valerie Curran, H; Burgess, Neil

    2015-11-01

    Alcohol is frequently involved in psychological trauma and often used by individuals to reduce fear and anxiety. We examined the effects of alcohol on fear acquisition and extinction within a virtual environment. Healthy volunteers were administered alcohol (0.4g/kg) or placebo and underwent acquisition and extinction from different viewpoints of a virtual courtyard, in which the conditioned stimulus, paired with a mild electric shock, was centrally located. Participants returned the following day to test fear recall from both viewpoints of the courtyard. Skin conductance responses were recorded as an index of conditioned fear. Successful fear acquisition under alcohol contrasted with impaired extinction learning evidenced by persistent conditioned responses (Experiment 1). Participants' impairments in extinction under alcohol correlated with impairments in remembering object-locations in the courtyard seen from one viewpoint when tested from the other viewpoint. Alcohol-induced extinction impairments were overcome by increasing the number of extinction trials (Experiment 2). However, a test of fear recall the next day showed persistent fear in the alcohol group across both viewpoints. Thus, alcohol impaired extinction rather than acquisition of fear, suggesting that extinction is more dependent than acquisition on alcohol-sensitive representations of spatial context. Overall, extinction learning under alcohol was slower, weaker and less context-specific, resulting in persistent fear at test that generalized to the extinction viewpoint. The selective effect on extinction suggests an effect of alcohol on prefrontal involvement, while the reduced context-specificity implicates the hippocampus. These findings have important implications for the use of alcohol by individuals with clinical anxiety disorders.

  10. Extinction learning as a moderator of d-cycloserine efficacy for enhancing exposure therapy in posttraumatic stress disorder.

    Science.gov (United States)

    de Kleine, Rianne A; Smits, Jasper A J; Hendriks, Gert-Jan; Becker, Eni S; van Minnen, Agnes

    2015-08-01

    Augmentation of exposure therapy with d-cycloserine (DCS) has proven efficacious across anxiety disorders, although results in PTSD have been mixed. Work in animals and anxiety-disordered patients suggest that the potentiating effects of DCS are dependent on the level of extinction learning during extinction training and exposure treatment, respectively. The aim of the current study was to replicate and extend previous work by examining the association between the degree of extinction learning and DCS efficacy in our randomized clinical trial on DCS (50 mg) versus placebo enhancement of exposure therapy in a chronic mixed-trauma PTSD sample (N=67; de Kleine, Hendriks, Kusters, Broekman, & van Minnen, 2012). The decline in subjective units of distress ratings collected during and across the exposure sessions were evaluated as indices of extinction learning. First, we examined whether extinction learning during an exposure session moderated DCS effects on self-reported PTSD symptoms at the next session. Second, we examined whether averaged extinction learning over the course of treatment interacted with group assignment to predict change over time and post treatment outcome. We did not find evidence that DCS effects were moderated by the degree of extinction learning, although, extinction learning was related to outcome regardless of group assignment. In PTSD, not one extinction-learning index has been consistently linked to DCS enhanced exposure treatment outcome. More (experimental) work needs to been done to unravel the complex interplay between extinction learning and DCS enhancement, especially in PTSD patients.

  11. Extinction learning deficit in a rodent model of attention-deficit hyperactivity disorder

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    Brackney Ryan J

    2012-12-01

    Full Text Available Abstract Background Deficient operant extinction has been hypothesized to be constitutive of ADHD dysfunction. In order to elucidate the behavioral mechanisms underlying this deficit, the performance of an animal model of ADHD, the spontaneously hypertensive rat (SHR, was compared against the performance of a control strain, the Wistar-Kyoto rat (WKY during extinction. Method Following extensive training of lever pressing under variable interval schedules of food reinforcement (reported previously, SHR and WKY rats were exposed to two sessions of extinction training. Extinction data was analyzed using the Dynamic Bi-Exponential Refractory Model (DBERM of operant performance. DBERM assumes that operant responses are organized in bouts separated by pauses; during extinction, bouts may decline across multiple dimensions, including frequency and length. DBERM parameters were estimated using hierarchical Bayesian modeling. Results SHR responded more than WKY during the first extinction session. DBERM parameter estimates revealed that, at the onset of extinction, SHR produced more response bouts than WKY. Over the course of extinction, response bouts progressively shortened for WKY but not for SHR. Conclusions Based on prior findings on the sensitivity of DBERM parameters to motivational and schedule manipulations, present data suggests that (1 more frequent response bouts in SHR are likely related to greater incentive motivation, and (2 the persistent length of bouts in SHR are likely related to a slower updating of the response-outcome association. Overall, these findings suggest specific motivational and learning deficits that may explain ADHD-related impairments in operant performance.

  12. Resting heart rate variability predicts safety learning and fear extinction in an interoceptive fear conditioning paradigm.

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    Meike Pappens

    Full Text Available This study aimed to investigate whether interindividual differences in autonomic inhibitory control predict safety learning and fear extinction in an interoceptive fear conditioning paradigm. Data from a previously reported study (N = 40 were extended (N = 17 and re-analyzed to test whether healthy participants' resting heart rate variability (HRV - a proxy of cardiac vagal tone - predicts learning performance. The conditioned stimulus (CS was a slight sensation of breathlessness induced by a flow resistor, the unconditioned stimulus (US was an aversive short-lasting suffocation experience induced by a complete occlusion of the breathing circuitry. During acquisition, the paired group received 6 paired CS-US presentations; the control group received 6 explicitly unpaired CS-US presentations. In the extinction phase, both groups were exposed to 6 CS-only presentations. Measures included startle blink EMG, skin conductance responses (SCR and US-expectancy ratings. Resting HRV significantly predicted the startle blink EMG learning curves both during acquisition and extinction. In the unpaired group, higher levels of HRV at rest predicted safety learning to the CS during acquisition. In the paired group, higher levels of HRV were associated with better extinction. Our findings suggest that the strength or integrity of prefrontal inhibitory mechanisms involved in safety- and extinction learning can be indexed by HRV at rest.

  13. Cocaine self-administration alters the relative effectiveness of multiple memory systems during extinction

    OpenAIRE

    Gabriele, Amanda; Setlow, Barry; Packard, Mark G.

    2009-01-01

    Rats were trained to run a straight-alley maze for an oral cocaine or sucrose vehicle solution reward, followed by either response or latent extinction training procedures that engage neuroanatomically dissociable “habit” and “cognitive” memory systems, respectively. In the response extinction condition, rats performed a runway approach response to an empty fluid well. In the latent extinction condition, rats were placed at the empty fluid well without performing a runway approach response. R...

  14. Behavioral and neurobiological mechanisms of extinction in Pavlovian and instrumental learning.

    Science.gov (United States)

    Todd, Travis P; Vurbic, Drina; Bouton, Mark E

    2014-02-01

    This article reviews research on the behavioral and neural mechanisms of extinction as it is represented in both Pavlovian and instrumental learning. In Pavlovian extinction, repeated presentation of a signal without its reinforcer weakens behavior evoked by the signal; in instrumental extinction, repeated occurrence of a voluntary action without its reinforcer weakens the strength of the action. In either case, contemporary research at both the behavioral and neural levels of analysis has been guided by a set of extinction principles that were first generated by research conducted at the behavioral level. The review discusses these principles and illustrates how they have informed the study of both Pavlovian and instrumental extinction. It shows that behavioral and neurobiological research efforts have been tightly linked and that their results are readily integrated. Pavlovian and instrumental extinction are also controlled by compatible behavioral and neural processes. Since many behavioral effects observed in extinction can be multiply determined, we suggest that the current close connection between behavioral-level and neural-level analyses will need to continue.

  15. Involvement of dopamine D1/D5 and D2 receptors in context-dependent extinction learning and memory reinstatement

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    Marion Agnes Emma Andre

    2016-01-01

    Full Text Available Dopamine contributes to the regulation of higher order information processing and executive control. It is important for memory consolidation processes, and for the adaptation of learned responses based on experience. In line with this, under aversive learning conditions, application of dopamine receptor antagonists prior to extinction result in enhanced memory reinstatement. Here, we investigated the contribution of the dopaminergic system to extinction and memory reinstatement (renewal of an appetitive spatial learning task in rodents. Rats were trained for 3 days in a T-maze (context ‘A’ to associate a goal arm with a food reward, despite low reward probability (acquisition phase. On day 4, extinction learning (unrewarded occurred, that was reinforced by a context change (‘B’. On day 5, re-exposure to the (unrewarded ‘A’-context took place (renewal of context ‘A’, followed by extinction of context ‘A’. In control animals, significant extinction occurred on day 4, that was followed by an initial memory reinstatement (renewal on day 5, that was, in turn, succeeded by extinction of renewal. Intracerebral treatment with a D1/D5-receptor antagonist prior to the extinction trials, elicited a potent enhancement of extinction in context ‘B’. By contrast, a D1/D5-agonist impaired renewal in context ’A’. Extinction in the ‘A’ context on day 5 was unaffected by the D1/D5-ligands. Treatment with a D2-receptor antagonist prior to extinction had no overall effect on extinction in context ‘B or renewal in context ‘A’, although extinction of the renewal effect was impaired on day 5, compared to controls.Taken together, these data suggest that dopamine acting on the D1/D5-receptor modulates both acquisition and consolidation of context-dependent extinction. By contrast, the D2-receptor may contribute to context-independent aspects of this kind of extinction learning.

  16. Involvement of Dopamine D1/D5 and D2 Receptors in Context-Dependent Extinction Learning and Memory Reinstatement

    Science.gov (United States)

    André, Marion Agnès Emma; Manahan-Vaughan, Denise

    2016-01-01

    Dopamine contributes to the regulation of higher order information processing and executive control. It is important for memory consolidation processes, and for the adaptation of learned responses based on experience. In line with this, under aversive learning conditions, application of dopamine receptor antagonists prior to extinction result in enhanced memory reinstatement. Here, we investigated the contribution of the dopaminergic system to extinction and memory reinstatement (renewal) of an appetitive spatial learning task in rodents. Rats were trained for 3 days in a T-maze (context “A”) to associate a goal arm with a food reward, despite low reward probability (acquisition phase). On day 4, extinction learning (unrewarded) occurred, that was reinforced by a context change (“B”). On day 5, re-exposure to the (unrewarded) “A” context took place (renewal of context “A”, followed by extinction of context “A”). In control animals, significant extinction occurred on day 4, that was followed by an initial memory reinstatement (renewal) on day 5, that was, in turn, succeeded by extinction of renewal. Intracerebral treatment with a D1/D5-receptor antagonist prior to the extinction trials, elicited a potent enhancement of extinction in context “B”. By contrast, a D1/D5-agonist impaired renewal in context “A”. Extinction in the “A” context on day 5 was unaffected by the D1/D5-ligands. Treatment with a D2-receptor antagonist prior to extinction had no overall effect on extinction in context “B” or renewal in context “A”, although extinction of the renewal effect was impaired on day 5, compared to controls. Taken together, these data suggest that dopamine acting on the D1/D5-receptor modulates both acquisition and consolidation of context-dependent extinction. By contrast, the D2-receptor may contribute to context-independent aspects of this kind of extinction learning. PMID:26834599

  17. Altered activity of the medial prefrontal cortex and amygdala during acquisition and extinction of an active avoidance task

    Directory of Open Access Journals (Sweden)

    Xilu eJiao

    2015-09-01

    Full Text Available Altered medial prefrontal cortex (mPFC and amygdala function is associated with anxiety-related disorders. While the mPFC-amygdala pathway has a clear role in fear conditioning, these structures are also involved in active avoidance. Given that avoidance perseveration represents a core symptom of anxiety disorders, the neural substrate of avoidance, especially its extinction, requires better understanding. The present study was designed to investigate the activity of mPFC and amygdala neurons during acquisition and extinction of lever-press avoidance in rats. In particular, neural activity was examined in the mPFC, intercalated cell clusters (ITCs, lateral (LA, basal (BA and central (CeA amygdala, at various time points during acquisition and extinction, using induction of the immediate early gene product, c-Fos. Neural activity was greater in the mPFC, LA, BA, and ITC during the extinction phase as compared to the acquisition phase. In contrast, the CeA was the only region that was more activated during acquisition than during extinction. Our results indicate that elevated activity in the mPFC, BA, LA and ITCs, and reduced CeA activity is associated with extinction of active avoidance. Moreover, inhibitory neurons are activated differently in the mPFC and BA during early and late phase of acquisition and extinction, suggesting their dynamic involvement in the development of avoidance response. Together, these data start to identify the key brain regions important in active avoidance behavior, areas that could be associated with avoidance perseveration in anxiety disorders.

  18. Cocaine Self-Administration Alters the Relative Effectiveness of Multiple Memory Systems during Extinction

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    Gabriele, Amanda; Setlow, Barry; Packard, Mark G.

    2009-01-01

    Rats were trained to run a straight-alley maze for an oral cocaine or sucrose vehicle solution reward, followed by either response or latent extinction training procedures that engage neuroanatomically dissociable "habit" and "cognitive" memory systems, respectively. In the response extinction condition, rats performed a runway approach response…

  19. Hyperresponsiveness of the Neural Fear Network During Fear Conditioning and Extinction Learning in Male Cocaine Users

    NARCIS (Netherlands)

    Kaag, A.M.; Levar, N.; Woutersen, K.; Homberg, J.R.; Brink, W. van den; Reneman, L.; Wingen, G. van

    2016-01-01

    OBJECTIVE: The authors investigated whether cocaine use disorder is associated with abnormalities in the neural underpinnings of aversive conditioning and extinction learning, as these processes may play an important role in the development and persistence of drug abuse. METHOD: Forty male regular c

  20. Learning and the persistence of appetite: extinction and the motivation to eat and overeat.

    Science.gov (United States)

    Bouton, Mark E

    2011-04-18

    The modern world is saturated with highly palatable and highly available food, providing many opportunities to associate food with environmental cues and actions (through Pavlovian and operant or instrumental learning, respectively). Basic learning processes can often increase the tendency to approach and consume food, whereas extinction, in which Pavlovian and operant behaviors decline when the reinforcer is withheld, weakens but does not erase those tendencies. Contemporary research suggests that extinction involves an inhibitory form of new learning that appears fragile because it is highly dependent on the context for expression. These ideas are supported by the phenomena of renewal, spontaneous recovery, resurgence, reinstatement, and rapid reacquisition in appetitive learning, which together may help explain why overeating may be difficult to suppress permanently, and why appetitive behavior may seem so persistent.

  1. Lesions of the lateral habenula facilitate active avoidance learning and threat extinction.

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    Song, Mihee; Jo, Yong Sang; Lee, Yeon-Kyung; Choi, June-Seek

    2017-02-01

    The lateral habenula (LHb) is an epithalamic brain structure that provides strong projections to midbrain monoaminergic systems that are involved in motivation, emotion, and reinforcement learning. LHb neurons are known to convey information about aversive outcomes and negative prediction errors, suggesting a role in learning from aversive events. To test this idea, we examined the effects of electrolytic lesions of the LHb on signaled two-way active avoidance learning in which rats were trained to avoid an unconditioned stimulus (US) by taking a proactive shuttling response to an auditory conditioned stimulus (CS). The lesioned animals learned the avoidance response significantly faster than the control groups. In a separate experiment, we also investigated whether the LHb contributes to Pavlovian threat (fear) conditioning and extinction. Following paired presentations of the CS and the US, LHb-lesioned animals showed normal acquisition of conditioned response (CR) measured with freezing. However, extinction of the CR in the subsequent CS-only session was significantly faster. The enhanced performance in avoidance learning and in threat extinction jointly suggests that the LHb normally plays an inhibitory role in learning driven by absence of aversive outcomes.

  2. Role of the hippocampus and amygdala in the extinction of fear-motivated learning.

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    Vianna, Monica R; Coitinho, Adriana S; Izquierdo, Ivan

    2004-01-01

    Fear-motivated learning is at the root of phobias, panic, generalized anxiety and the posttraumatic stress disorder. This makes the inhibition of fear-motivated behavior a therapeutic desideratum in these diseases. The simplest way to accomplish this is by extinction, a procedure by which a given association between a conditioned stimulus or context (CS) and a fearsome event is replaced by a new association between the CS and the lack of the fearsome stimulus. This is a new learning for the subject and, in rats, it requires gene expression and protein synthesis both in the hippocampus and the basolateral amygdala, alongside with the activation of various metabolic signaling pathways. These requirements are similar to, but not identical with those for consolidation of the original memory. In addition, some systems uninvolved in original consolidation appear to be involved in extinction, namely, the endocannabinoid system. Extinction can be enhanced by prolonging the exposure to the lack of fearsome stimulation; e.g., in rats, by increasing the time of permanence in the compartment where the animals no longer receive a footshock. Further research into the possibilities of enhancing extinction at the expense of the original fearsome learning is desirable.

  3. Extinction learning, which consists of the inhibition of retrieval, can be learned without retrieval.

    Science.gov (United States)

    de Carvalho Myskiw, Jociane; Furini, Cristiane Regina Guerino; Schmidt, Bianca; Ferreira, Flávia; Izquierdo, Ivan

    2015-01-13

    In the present study we test the hypothesis that extinction is not a consequence of retrieval in unreinforced conditioned stimulus (CS) presentation but the mere perception of the CS in the absence of a conditioned response. Animals with cannulae implanted in the CA1 region of hippocampus were subjected to extinction of contextual fear conditioning. Muscimol infused intra-CA1 before an extinction training session of contextual fear conditioning (CFC) blocks retrieval but not consolidation of extinction measured 24 h later. Additionally, this inhibition of retrieval does not affect early persistence of extinction when tested 7 d later or its spontaneous recovery after 2 wk. Furthermore, both anisomycin, an inhibitor of ribosomal protein synthesis, and rapamycin, an inhibitor of extraribosomal protein synthesis, given into the CA1, impair extinction of CFC regardless of whether its retrieval was blocked by muscimol. Therefore, retrieval performance in the first unreinforced session is not necessary for the installation, maintenance, or spontaneous recovery of extinction of CFC.

  4. Distinct Contributions of the Basolateral Amygdala and the Medial Prefrontal Cortex to Learning and Relearning Extinction of Context Conditioned Fear

    Science.gov (United States)

    Laurent, Vincent; Westbrook, R. Frederick

    2008-01-01

    We studied the roles of the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) in learning and relearning to inhibit context conditioned fear (freezing) in extinction. In Experiment 1, pre-extinction BLA infusion of the NMDA receptor (NMDAr) antagonist, ifenprodil, impaired the development and retention of inhibition but…

  5. Autophosphorylation of [alpha]CaMKII is Differentially Involved in New Learning and Unlearning Mechanisms of Memory Extinction

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    Kimura, Ryoichi; Silva, Alcino J.; Ohno, Masuo

    2008-01-01

    Accumulating evidence indicates the key role of [alpha]-calcium/calmodulin-dependent protein kinase II ([alpha]CaMKII) in synaptic plasticity and learning, but it remains unclear how this kinase participates in the processing of memory extinction. Here, we investigated the mechanism by which [alpha]CaMKII may mediate extinction by using…

  6. EtOH self-administration on shuttle box avoidance learning and extinction in rats.

    Science.gov (United States)

    Pallarés, M A; Nadal, R A; Hernández-Torres, M; Ferré, N A

    1997-01-01

    The effects of ethanol on the acquisition and extinction of the two-way active avoidance response were examined in adult, male Wistar rats from two treatment groups, oral self-administration of alcohol solution (10% v/v ethanol and 3% w/v glucose in distilled water) and oral self-administration of control solution (3% w/v glucose in distilled water). Alcohol or control solutions were available 1 h per day during 15 days simultaneously with food, with free water for the rest of the day. Blood was drawn in the last day of this phase to evaluate blood ethanol levels (BEL). After this period, rats were tested in a two-bottle paradigm for 1 h per day and placed in a shuttle box immediately afterwards. This phase went lasted for 10 days. Subjects were trained to avoid an electric foot shock in the first 5 days (15 trials per day). Following this, half of the subjects were tested in an "easy extinction with punishment" (EEP) and the other half in a "difficult extinction with punishment" (DEP) of the avoidance response for the last 5 days. Alcohol accelerates the avoidance responding acquisition, and no significant effects of alcohol were seen in the extinction phase. Data are discussed in terms of the specificity of the effects of alcohol on learning.

  7. Contextual change after fear acquisition affects conditioned responding and the time course of extinction learning – Implications for renewal research

    Directory of Open Access Journals (Sweden)

    Rachel eSjouwerman

    2015-12-01

    Full Text Available Context plays a central role in retrieving (fear memories. Accordingly, context manipulations are inherent to most return of fear (ROF paradigms (in particular renewal, involving contextual changes after fear extinction. Context changes are, however, also often embedded during earlier stages of ROF experiments such as context changes between fear acquisition and extinction (e.g. in ABC and ABA renewal. Previous studies using these paradigms have however focused exclusively on the context switch after extinction (i.e. renewal. Thus, the possibility of a general effect of a context switch on conditioned responding that may not be conditional to preceding extinction learning remains unstudied.Hence, the current study investigated the impact of a context switch between fear acquisition and extinction on immediate conditioned responding and on the time-course of extinction learning by using a multimodal approach. A group that underwent contextual change after fear conditioning (AB; n = 36 was compared with a group without a contextual change from acquisition to extinction (AA; n = 149, while measuring autonomic (skin conductance and fear potentiated startle measures and subjective fear ratings. Contextual change between fear acquisition and extinction had a pronounced effect on both immediate conditioned responding and on the time course of extinction learning in skin conductance responses and subjective fear ratings. This may have important implications for the mechanisms underlying and the interpretation of the renewal effect (i.e. contextual switch after extinction. Consequently, future studies should incorporate designs and statistical tests that disentangle general effects of contextual change from genuine ROF effects.

  8. Learning to forget: manipulating extinction and reconsolidation processes to treat addiction.

    Science.gov (United States)

    Torregrossa, Mary M; Taylor, Jane R

    2013-04-01

    Finding effective long-lasting treatments for drug addiction has been an elusive goal. Consequently, researchers are beginning to investigate novel treatment strategies including manipulations of drug-associated memories. When environmental stimuli (cues) become associated with drug use, they become powerful motivators of continued drug use and relapse after abstinence. Reducing the strength of these cue-drug memories could decrease the number of factors that induce craving and relapse to aid in the treatment of addiction. Enhancing the consolidation of extinction learning and/or disrupting cue-drug memory reconsolidation are two strategies that have been proposed to reduce the strength of cues in motivating drug-seeking and drug-taking behavior. Here, we review the latest basic and clinical research elucidating the mechanisms underlying consolidation of extinction and reconsolidation of cue-drug memories in the hopes of developing pharmacological tools that exploit these signaling systems to treat addiction.

  9. Extinction-dependent alterations in corticostriatal mGluR2/3 and mGluR7 receptors following chronic methamphetamine self-administration in rats.

    Science.gov (United States)

    Schwendt, Marek; Reichel, Carmela M; See, Ronald E

    2012-01-01

    Methamphetamine (meth) is a highly addictive and widely abused psychostimulant. Repeated use of meth can quickly lead to dependence, and may be accompanied by a variety of persistent psychiatric symptoms and cognitive impairments. The neuroadaptations underlying motivational and cognitive deficits produced by chronic meth intake remain poorly understood. Altered glutamate neurotransmission within the prefrontal cortex (PFC) and striatum has been linked to both persistent drug-seeking and cognitive dysfunction. Therefore, the current study investigated changes in presynaptic mGluR receptors within corticostriatal circuitry after extended meth self-administration. Rats self-administered meth (or received yoked-saline) in 1 hr/day sessions for 7 days (short-access) followed by 14 days of 6 hrs/day (long-access). Rats displayed a progressive escalation of daily meth intake up to 6 mg/kg per day. After cessation of meth self-administration, rats underwent daily extinction or abstinence without extinction training for 14 days before being euthanized. Synaptosomes from the medial PFC, nucleus accumbens (NAc), and the dorsal striatum (dSTR) were isolated and labeled with membrane-impermeable biotin in order to measure surface mGluR2/3 and mGluR7 receptors. Extended access to meth self-administration followed by abstinence decreased surface and total levels of mGluR2/3 receptors in the NAc and dSTR, while in the PFC, only a loss of surface mGluR2/3 and mGluR7 receptors was detected. Daily extinction trials reversed the downregulation of mGluR2/3 receptors in the NAc and dSTR and mGluR7 in the PFC, but downregulation of surface mGluR2/3 receptors in the PFC was present regardless of post-meth experience. Thus, extinction learning can selectively restore some populations of downregulated mGluRs after prolonged exposure to meth. The present findings could have implications for our understanding of the persistence (or recovery) of meth-induced motivational and cognitive

  10. Extinction-dependent alterations in corticostriatal mGluR2/3 and mGluR7 receptors following chronic methamphetamine self-administration in rats.

    Directory of Open Access Journals (Sweden)

    Marek Schwendt

    Full Text Available Methamphetamine (meth is a highly addictive and widely abused psychostimulant. Repeated use of meth can quickly lead to dependence, and may be accompanied by a variety of persistent psychiatric symptoms and cognitive impairments. The neuroadaptations underlying motivational and cognitive deficits produced by chronic meth intake remain poorly understood. Altered glutamate neurotransmission within the prefrontal cortex (PFC and striatum has been linked to both persistent drug-seeking and cognitive dysfunction. Therefore, the current study investigated changes in presynaptic mGluR receptors within corticostriatal circuitry after extended meth self-administration. Rats self-administered meth (or received yoked-saline in 1 hr/day sessions for 7 days (short-access followed by 14 days of 6 hrs/day (long-access. Rats displayed a progressive escalation of daily meth intake up to 6 mg/kg per day. After cessation of meth self-administration, rats underwent daily extinction or abstinence without extinction training for 14 days before being euthanized. Synaptosomes from the medial PFC, nucleus accumbens (NAc, and the dorsal striatum (dSTR were isolated and labeled with membrane-impermeable biotin in order to measure surface mGluR2/3 and mGluR7 receptors. Extended access to meth self-administration followed by abstinence decreased surface and total levels of mGluR2/3 receptors in the NAc and dSTR, while in the PFC, only a loss of surface mGluR2/3 and mGluR7 receptors was detected. Daily extinction trials reversed the downregulation of mGluR2/3 receptors in the NAc and dSTR and mGluR7 in the PFC, but downregulation of surface mGluR2/3 receptors in the PFC was present regardless of post-meth experience. Thus, extinction learning can selectively restore some populations of downregulated mGluRs after prolonged exposure to meth. The present findings could have implications for our understanding of the persistence (or recovery of meth-induced motivational and

  11. Positive allosteric modulation of mGluR5 accelerates extinction learning but not relearning following methamphetamine self-administration

    Directory of Open Access Journals (Sweden)

    Peter R Kufahl

    2012-11-01

    Full Text Available Recent studies have implicated glutamate neurotransmission as an important substrate for the extinction of conditioned behaviors, including responding for drug reinforcement. Positive allosteric modulation of the type-5 metabotropic glutamate receptor (mGluR5 in particular has emerged as a treatment strategy for the enhancement of extinction of drug-motivated behaviors. Here, we investigated the effects of the mGluR5 positive allosteric modulator CDPPB, a compound known for its cognitive enhancing effects in rodents, on extinction learning in rats with different histories of methamphetamine (METH training. Rats were trained to self-administer METH under two conditions: 16 daily sessions of short access (90 min/day, ShA, or 8 daily sessions of short access followed by 8 sessions of long access (6 hr/day, LgA. Control rats self-administered sucrose pellets in daily 30 min sessions. Next, rats were administered vehicle or 30 mg/kg CDPPB prior to 7 consecutive daily extinction sessions, subjected to additional extinction sessions to re-establish a post-treatment baseline, and then tested for reinstatement of behavior in the presence of METH- or sucrose-paired cues. Rats were then subjected to a second series of extinction sessions, preceded by vehicle or 30 mg/kg CDPPB, and an additional test for cue-triggered reinstatement. CDPPB treatment resulted in a more rapid extinction of responding on the active lever, especially in the early sessions of the first extinction sequence. However, treatment effects were minimal during subsequent cue reinstatement tests and nonexistent during the second series of extinction sessions. Rats with histories of ShA, LgA and sucrose training expressed similar behavioral sensitivities to CDPPB, with LgA rats demonstrating a modestly higher treatment effect. Positive allosteric modulation of mGluR5 may therefore have some beneficial effects on efforts to facilitate extinction learning and reduce methamphetamine seeking.

  12. Can previous learning alter future plasticity mechanisms?

    Science.gov (United States)

    Crestani, Ana Paula; Quillfeldt, Jorge Alberto

    2016-02-01

    The dynamic processes related to mnemonic plasticity have been extensively researched in the last decades. More recently, studies have attracted attention because they show an unusual plasticity mechanism that is independent of the receptor most usually related to first-time learning--that is, memory acquisition-the NMDA receptor. An interesting feature of this type of learning is that a previous experience may cause modifications in the plasticity mechanism of a subsequent learning, suggesting that prior experience in a very similar task triggers a memory acquisition process that does not depend on NMDARs. The intracellular molecular cascades necessary to assist the learning process seem to depend on the activation of hippocampal CP-AMPARs. Moreover, most of these studies were performed on hippocampus-dependent tasks, even though other brain areas, such as the basolateral amygdala, also display NMDAR-independent learning.

  13. Avoidance prone individuals self reporting behavioral inhibition exhibit facilitated acquisition and altered extinction of conditioned eyeblinks with partial reinforcement schedules.

    Science.gov (United States)

    Allen, Michael Todd; Myers, Catherine E; Servatius, Richard J

    2014-01-01

    Avoidance in the face of novel situations or uncertainty is a prime feature of behavioral inhibition which has been put forth as a risk factor for the development of anxiety disorders. Recent work has found that behaviorally inhibited (BI) individuals acquire conditioned eyeblinks faster than non-inhibited (NI) individuals in omission and yoked paradigms in which the predictive relationship between the conditioned stimulus (CS) and unconditional stimulus (US) is less than optimal as compared to standard training with CS-US paired trials (Holloway et al., 2014). In the current study, we tested explicitly partial schedules in which half the trials were CS alone or US alone trials in addition to the standard CS-US paired trials. One hundred and forty nine college-aged undergraduates participated in the study. All participants completed the Adult Measure of Behavioral Inhibition (i.e., AMBI) which was used to group participants as BI and NI. Eyeblink conditioning consisted of three US alone trials, 60 acquisition trials, and 20 CS-alone extinction trials presented in one session. Conditioning stimuli were a 500 ms tone CS and a 50-ms air puff US. Behaviorally inhibited individuals receiving 50% partial reinforcement with CS alone or US alone trials produced facilitated acquisition as compared to NI individuals. A partial reinforcement extinction effect (PREE) was evident with CS alone trials in BI but not NI individuals. These current findings indicate that avoidance prone individuals self-reporting behavioral inhibition over-learn an association and are slow to extinguish conditioned responses (CRs) when there is some level of uncertainty between paired trials and CS or US alone presentations.

  14. Avoidance Prone Individuals Self Reporting Behavioral Inhibition Exhibit Facilitated Acquisition and Altered Extinction of Conditioned Eyeblinks With Partial Reinforcement Schedules

    Directory of Open Access Journals (Sweden)

    Michael Todd Allen

    2014-10-01

    Full Text Available Avoidance in the face of novel situations or uncertainty is a prime feature of behavioral inhibition which has been put forth as a risk factor for the development of anxiety disorders. Recent work has found that behaviorally inhibited individuals acquire conditioned eyeblinks faster than non-inhibited individuals in omission and yoked paradigms in which the predictive relationship between the conditioned stimulus (CS and unconditional stimulus (US is less than optimal as compared to standard training with CS-US paired trials (Holloway et al., 2014. In the current study, we tested explicitly partial schedules in which half the trials were CS alone or US alone trials in addition to the standard CS-US paired trials. One hundred and forty nine college-aged undergraduates participated in the study. All participants completed the Adult Measure of Behavioral Inhibition (i.e., AMBI which was used to group participants as behaviorally inhibited and non-inhibited. Eyeblink conditioning consisted of 3 US alone trials, 60 acquisition trials, and 20 CS-alone extinction trials presented in one session. Conditioning stimuli were a 500 ms tone conditioned stimulus (CS and a 50-ms air puff unconditional stimulus (US. Behaviorally inhibited individuals receiving 50% partial reinforcement with CS alone or US alone trials produced facilitated acquisition as compared to non-inhibited individuals. A partial reinforcement extinction effect was evident with CS alone trials in behaviorally inhibited but not non-inhibited individuals. These current findings indicate that avoidance prone individuals self-reporting behavioral inhibition over-learn an association and are slow to extinguish conditioned responses when there is some level of uncertainty between paired trials and CS or US alone presentations.

  15. Systemic or Intra-Amygdala Infusion of the Benzodiazepine, Midazolam, Impairs Learning, but Facilitates Re-Learning to Inhibit Fear Responses in Extinction

    Science.gov (United States)

    Hart, Genevra; Harris, Justin A.; Westbrook, R. Frederick

    2010-01-01

    A series of experiments used rats to study the effect of a systemic or intra-amygdala infusion of the benzodiazepine, midazolam, on learning and re-learning to inhibit context conditioned fear (freezing) responses. Rats were subjected to two context-conditioning episodes followed by extinction under drug or vehicle, or to two cycles of context…

  16. Learning and extinction of a passive avoidance response in mice with high levels of predisposition to catalepsy.

    Science.gov (United States)

    Dubrovina, N I; Zinov'ev, D R; Zinov'eva, D V; Kulikov, A V

    2009-06-01

    This report presents results obtained from comparative analysis of learning and the dynamics of extinction of a conditioned passive avoidance response in ASC mice, which were bred for a high level of predisposition to catalepsy, and in CBA and AKR mice. The following findings were obtained: 1) impairments to the extinction of the memory of fear represent an important symptom of depression in ASC mice; 2) extinction is delayed in CBA mice; and 3) new inhibitory learning occurs quickly in AKR mice. Prolonged retention of the fear memory in ASC mice appears to be related to increased anxiety on prolonged testing without a punishment. The deficit of inhibition of the fear reaction in ASC mice allows this strain to be regarded as a genetic model of depression.

  17. Partial reinforcement effects on learning and extinction of place preferences in the water maze.

    Science.gov (United States)

    Prados, José; Sansa, Joan; Artigas, Antonio A

    2008-11-01

    In two experiments, two groups of rats were trained in a navigation task according to either a continuous or a partial schedule of reinforcement. In Experiment 1, animals that were given continuous reinforcement extinguished the spatial response of approaching the goal location more readily than animals given partial reinforcement-a partial reinforcement extinction effect. In Experiment 2, after partially or continuously reinforced training, animals were trained in a new task that made use of the same reinforcer according to a continuous reinforcement schedule. Animals initially given partial reinforcement performed better in the novel task than did rats initially given continuous reinforcement. These results replicate, in the spatial domain, well-known partial reinforcement phenomena typically observed in the context of Pavlovian and instrumental conditioning, suggesting that similar principles govern spatial and associative learning. The results reported support the notion that salience modulation processes play a key role in determining partial reinforcement effects.

  18. Extinction learning as a moderator of d-cycloserine efficacy for enhancing exposure therapy in posttraumatic stress disorder

    NARCIS (Netherlands)

    Kleine, R.A. de; Smits, J.A.; Hendriks, G.J.; Becker, E.S.; Minnen, A. van

    2015-01-01

    Augmentation of exposure therapy with d-cycloserine (DCS) has proven efficacious across anxiety disorders, although results in PTSD have been mixed. Work in animals and anxiety-disordered patients suggest that the potentiating effects of DCS are dependent on the level of extinction learning during e

  19. Social stress reactivity alters reward and punishment learning.

    Science.gov (United States)

    Cavanagh, James F; Frank, Michael J; Allen, John J B

    2011-06-01

    To examine how stress affects cognitive functioning, individual differences in trait vulnerability (punishment sensitivity) and state reactivity (negative affect) to social evaluative threat were examined during concurrent reinforcement learning. Lower trait-level punishment sensitivity predicted better reward learning and poorer punishment learning; the opposite pattern was found in more punishment sensitive individuals. Increasing state-level negative affect was directly related to punishment learning accuracy in highly punishment sensitive individuals, but these measures were inversely related in less sensitive individuals. Combined electrophysiological measurement, performance accuracy and computational estimations of learning parameters suggest that trait and state vulnerability to stress alter cortico-striatal functioning during reinforcement learning, possibly mediated via medio-frontal cortical systems.

  20. Artificial neural networks can learn to estimate extinction rates from molecular phylogenies

    NARCIS (Netherlands)

    Bokma, Folmer

    2006-01-01

    Molecular phylogenies typically consist of only extant species, yet they allow inference of past rates of extinction, because. recently originated species are less likely to be extinct than ancient species. Despite the simple structure of the assumed underlying speciation-extinction process, paramet

  1. Translation of associative learning models into extinction reminders delivered via mobile phones during cue exposure interventions for substance use.

    Science.gov (United States)

    Rosenthal, M Zachary; Kutlu, Munir G

    2014-09-01

    Despite experimental findings and some treatment research supporting the use of cues as a means to induce and extinguish cravings, interventions using cue exposure have not been well integrated into contemporary substance abuse treatments. A primary problem with exposure-based interventions for addiction is that after learning not to use substances in the presence of addiction cues inside the clinic (i.e., extinction), stimuli in the naturalistic setting outside the clinic may continue to elicit craving, drug use, or other maladaptive conditioned responses. For exposure-based substance use interventions to be efficacious, new approaches are needed that can prevent relapse by directly generalizing learning from the therapeutic setting into naturalistic settings associated with a high risk for relapse. Basic research suggests that extinction reminders (ERs) can be paired with the context of learning new and more adaptive conditioned responses to substance abuse cues in exposure therapies for addiction. Using mobile phones and automated dialing and data collection software, ERs can be delivered in everyday high-risk settings to inhibit conditioned responses to substance-use-related stimuli. In this review, we describe how associative learning mechanisms (e.g., conditioned inhibition) can inform how ERs are conceptualized, learned, and implemented to prevent substance use when delivered via mobile phones. This approach, exposure with portable reminders of extinction, is introduced as an adjunctive intervention that uses brief automated ERs between clinic visits when individuals are in high-risk settings for drug use.

  2. Selegiline modifies the extinction of responding following morphine self-administration, but does not alter cue-induced reinstatement, reacquisition of morphine reinforcement, or precipitated withdrawal.

    Science.gov (United States)

    Grasing, Kenneth; He, Shaunteng; Li, Ning

    2005-01-01

    Selegiline is an irreversible inhibitor of monoamine oxidase (MAO) with psychostimulant and neuroprotective effects which can prevent decreases in dopamine efflux that follow opiate withdrawal. The present study evaluated effects of selegiline treatment on morphine-seeking behavior and morphine reinforcement in Wistar rats (n = 26). In additional animals (n = 30), the ability of single doses of selegiline to modify naloxone-precipitated withdrawal was determined. After pretreatment with noncontingent morphine to establish opiate dependence, rats acquired self-administration of intravenous morphine. Daily intravenous treatment with saline or 2.0mg kg(-1) doses of selegiline was then initiated and continued over 14 days during extinction, reinstatement, and reacquisition of morphine self-administration. To reduce the potential for psychostimulant effects, selegiline was administered approximately 1h following self-administration, extinction, or reinstatement sessions. In some animals (n = 23), effects of saline or selegiline administration on locomotor activity were determined following extinction sessions. Daily selegiline treatment decreased the number of ratios completed and increased response latency during extinction, without modifying these measures during reinstatement or reacquisition of morphine self-administration. Chronic selegiline treatment increased locomotor activity recorded between 4 and 7h after selegiline administration on day 7 of extinction, but otherwise did not alter locomotor activity. Pretreatment with single, 2.0mg kg(-1) doses of selegiline did not modify naloxone-precipitated withdrawal. In conclusion, pretreatment with selegiline produced only a small decrease in responding during extinction of morphine self-administration and did not modify cue-induced reinstatement of morphine-seeking behavior, reacquisition or morphine reinforcement, or precipitated withdrawal.

  3. Early age-dependent impairments of context-dependent extinction learning, object recognition, and object-place learning occur in rats.

    Science.gov (United States)

    Wiescholleck, Valentina; Emma André, Marion Agnès; Manahan-Vaughan, Denise

    2014-03-01

    The hippocampus is vulnerable to age-dependent memory decline. Multiple forms of memory depend on adequate hippocampal function. Extinction learning comprises active inhibition of no longer relevant learned information concurrent with suppression of a previously learned reaction. It is highly dependent on context, and evidence exists that it requires hippocampal activation. In this study, we addressed whether context-based extinction as well as hippocampus-dependent tasks, such as object recognition and object-place recognition, are equally affected by moderate aging. Young (7-8 week old) and older (7-8 month old) Wistar rats were used. For the extinction study, animals learned that a particular floor context indicated that they should turn into one specific arm (e.g., left) to receive a food reward. On the day after reaching the learning criterion of 80% correct choices, the floor context was changed, no reward was given and animals were expected to extinguish the learned response. Both, young and older rats managed this first extinction trial in the new context with older rats showing a faster extinction performance. One day later, animals were returned to the T-maze with the original floor context and renewal effects were assessed. In this case, only young but not older rats showed the expected renewal effect (lower extinction ratio as compared to the day before). To assess general memory abilities, animals were tested in the standard object recognition and object-place memory tasks. Evaluations were made at 5 min, 1 h and 7 day intervals. Object recognition memory was poor at short-term and intermediate time-points in older but not young rats. Object-place memory performance was unaffected at 5 min, but impaired at 1 h in older but not young rats. Both groups were impaired at 7 days. These findings support that not only aspects of general memory, but also context-dependent extinction learning, are affected by moderate aging. This may reflect less flexibility in

  4. Temporal Dynamics of Recovery from Extinction Shortly after Extinction Acquisition

    Science.gov (United States)

    Archbold, Georgina E.; Dobbek, Nick; Nader, Karim

    2013-01-01

    Evidence suggests that extinction is new learning. Memory acquisition involves both short-term memory (STM) and long-term memory (LTM) components; however, few studies have examined early phases of extinction retention. Retention of auditory fear extinction was examined at various time points. Shortly (1-4 h) after extinction acquisition…

  5. Interoceptive conditioning with the nicotine stimulus: extinction learning as a method for assessing stimulus similarity across doses.

    Science.gov (United States)

    Polewan, Robert J; Savala, Stephanie A; Bevins, Rick A

    2013-02-01

    Interoceptive conditioning involving the nicotine stimulus likely contributes to chronic tobacco use. To better understand the nature of this interoceptive conditioning, we compared generalization during repeated extinction with generalization in a 'transfer of extinction' test using a wide range of test doses. Rats were first trained in the discriminated goal-tracking task in which nicotine (0.2 or 0.4 mg/kg), but not saline, was paired with repeated intermittent access to sucrose. Across sessions, nicotine acquired control of approach behavior directed at the location of previous sucrose deliveries. Extinction followed with eight 20-min sessions without sucrose access; extinction doses of nicotine ranged from 0.05 to 0.6 mg/kg. In rats trained with 0.4 mg/kg, the 0.1, 0.2, and 0.6 mg/kg doses evoked comparable responding across extinction sessions; substitution was only partial at 0.05 and 0.075 mg/kg (i.e. above saline controls, but less than the training dose). With the 0.2 mg/kg training dose, complete generalization was seen only at the 0.1 and 0.4 mg/kg doses. After extinction, rats were given a transfer test with their training dose. Rats trained with 0.4 mg/kg showed full transfer of extinction learning with 0.1, 0.2, and 0.6 mg/kg (i.e. responding comparable with extinction with the training dose). Partial transfer was observed at 0.075 mg/kg. With the 0.2 mg/kg nicotine dose, only 0.4 mg/kg fully generalized; 0.075, 0.1, and 0.6 mg/kg showed partial transfer. Extinction with 0.05 mg/kg dose did not show transfer to either training dose. These findings indicated that conclusions regarding stimulus similarity across nicotine doses can vary with testing protocol.

  6. Heterogeneity in Threat Extinction Learning: Substantive and Methodological Considerations for Identifying Individual Difference in Response to Stress

    Directory of Open Access Journals (Sweden)

    Isaac Robert Galatzer-Levy

    2013-05-01

    Full Text Available Pavlovian threat (fear conditioning (PTC is an experimental paradigm that couples innate aversive stimuli with neutral cues to elicit learned defensive behavior in response to the neutral cue. PTC is commonly used as a translational model to study neurobiological and behavioral aspects of fear and anxiety disorders, including Posttraumatic Stress Disorder (PTSD. Though PTSD is a complex, multi-faceted construct that cannot be fully captured in animals, PTC is a conceptually valid model for studying the development and maintenance of learned threat responses. Thus it can inform the understanding of PTSD symptomatology. However, there are significant individual differences in posttraumatic stress that are not as of yet accounted for in studies of PTC. Individuals exposed to danger have been shown to follow distinct patterns: some adapt rapidly and completely (resilience, others adapt slowly (recovery, and others failure to adapt (chronic stress response. Identifying similar behavioral outcomes in PTC increases the translatability of this model. In this report, we present a flexible methodology for identifying individual differences in PTC by modeling latent subpopulations, or classes, characterized by defensive behavior during training. We provide evidence from a reanalysis of previously examined PTC learning and extinction data in rats to demonstrate the effectiveness of this methodology in identifying outcomes analogous to those observed in humans exposed to threat. By utilizing Latent Class Growth Analysis to test for heterogeneity in freezing behavior during threat conditioning and extinction learning in adult male outbred rats (n =58, three outcomes were identified: rapid extinction (57.3%, slow extinction (32.3%, and failure to extinguish (10.3%, indicating that heterogeneity analogous to that in naturalistic human studies is present in experimental animal studies, strengthening their translatability in understanding stress responses in

  7. Learning and memory in conditioned fear extinction: effects of d-cycloserine

    NARCIS (Netherlands)

    B. Vervliet

    2008-01-01

    This review addresses the effects of the cognitive enhancer D-cycloserine (DCS) on the memory processes that occur in conditioned fear extinction, which is the experimental model for exposure techniques to reduce clinical anxiety. All reported rat studies show an enhanced fear extinction effect when

  8. Chlordiazepoxide-induced released responding in extinction and punishment-conflict procedures is not altered by neonatal forebrain norepinephrine depletion.

    Science.gov (United States)

    Bialik, R J; Pappas, B A; Pusztay, W

    1982-02-01

    The effects of chlordiazepoxide (CDZ) in extinction and punishment-conflict tasks were examined in rats after neonatal systemic administration of 6-hydroxydopamine (6-OHDA) to deplete forebrain norepinephrine (NE). At about 70 days of age the rats were water deprived and trained for three days to drink in a novel apparatus. On the fourth day (test day) drinking was either extinguished by elimination of water from the drinking tube or punished by lick-contingent shock. Just prior to this test session half of the vehicle and half of the 6-OHDA treated rats were given an injection of CDZ (8 mg/kg IP). Both the injection of CDZ and forebrain NE depletion prolonged responding during extinction and reduced the suppressant effects of punishment in male rats, and these effects were of similar magnitude. Furthermore, CDZ was as effective in neonatal 6-OHDA treated male rats as in vehicle treated rats indicating that decreased transmission is ascending NE fibers caused by CDZ is not solely responsible for its behavioral effects in extinction and conflict tasks. Rather, these effects may involve cooperative mediation by both noradrenergic and serotonergic forebrain terminals. Unexpectedly, CDZ's anti-extinction effect was absent in female rats and its anti-conflict effect observed only in NE depleted females.

  9. AX+, BX- Discrimination Learning in the Fear-Potentiated Startle Paradigm: Possible Relevance to Inhibitory Fear Learning in Extinction

    Science.gov (United States)

    Myers, Karyn M.; Davis, Michael

    2004-01-01

    The neural mechanisms of fear suppression most commonly are studied through the use of extinction, a behavioral procedure in which a feared stimulus (i.e., one previously paired with shock) is nonreinforced repeatedly, leading to a reduction or elimination of the fear response. Although extinction is perhaps the most convenient index of fear…

  10. Extinction learning deficit in a rodent model of attention-deficit hyperactivity disorder

    OpenAIRE

    Brackney Ryan J; Cheung Timothy HC; Herbst Katrina; Hill Jade C; Sanabria Federico

    2012-01-01

    Abstract Background Deficient operant extinction has been hypothesized to be constitutive of ADHD dysfunction. In order to elucidate the behavioral mechanisms underlying this deficit, the performance of an animal model of ADHD, the spontaneously hypertensive rat (SHR), was compared against the performance of a control strain, the Wistar-Kyoto rat (WKY) during extinction. Method Following extensive training of lever pressing under variable interval schedules of food reinforcement (reported pre...

  11. Amphibian decline and extinction: what we know and what we need to learn.

    Science.gov (United States)

    Collins, James P

    2010-11-01

    For over 350 million yr, thousands of amphibian species have lived on Earth. Since the 1980s, amphibians have been disappearing at an alarming rate, in many cases quite suddenly. What is causing these declines and extinctions? In the modern era (post 1500) there are 6 leading causes of biodiversity loss in general, and all of these acting alone or together are responsible for modern amphibian declines: commercial use; introduced/exotic species that compete with, prey on, and parasitize native frogs and salamanders; land use change; contaminants; climate change; and infectious disease. The first 3 causes are historical in the sense that they have been operating for hundreds of years, although the rate of change due to each accelerated greatly after about the mid-20th century. Contaminants, climate change, and emerging infectious diseases are modern causes suspected of being responsible for the so-called 'enigmatic decline' of amphibians in protected areas. Introduced/exotic pathogens, land use change, and infectious disease are the 3 causes with a clear role in amphibian decline as well as extinction; thus far, the other 3 causes are only implicated in decline and not extinction. The present work is a review of the 6 causes with a focus on pathogens and suggested areas where new research is needed. Batrachochytrium dendrobatidis (Bd) is a chytrid fungus that is an emerging infectious disease causing amphibian population decline and species extinction. Historically, pathogens have not been seen as a major cause of extinction, but Bd is an exception, which is why it is such an interesting, important pathogen to understand. The late 20th and early 21st century global biodiversity loss is characterized as a sixth extinction event. Amphibians are a striking example of these losses as they disappear at a rate that greatly exceeds historical levels. Consequently, modern amphibian decline and extinction is a lens through which we can view the larger story of biodiversity

  12. Modern examples of extinctions

    DEFF Research Database (Denmark)

    Lövei, Gabor L

    2013-01-01

    reasons (certain groups do not fossilize) and methodological problems (methods of excavation and identification). Consequently, we can only crudely estimate the current rate of extinction. Nonetheless, it is evident that humans generated a new mass extinction, affecting all species in all habitats, and......No species lives forever, and extinction is the ultimate fate of all living species. The fossil record indicates that a recent extinction wave affecting terrestrial vertebrates was parallel with the arrival of modern humans to areas formerly uninhabited by them. These modern instances of extinction...... started at around 40,000 years ago. On continents, large mammals (especially those >50 kg body mass) were affected, while on islands, the impacts were mainly felt by birds. The causes of these extinctions are not well known but hunting, habitat alteration and the introduction of non-native species...

  13. Adolescents exhibit behavioral differences from adults during instrumental learning and extinction.

    Science.gov (United States)

    Sturman, David A; Mandell, Daniel R; Moghaddam, Bita

    2010-02-01

    Adolescence is associated with the development of brain regions linked to cognition and emotion. Such changes are thought to contribute to the behavioral and neuropsychiatric vulnerabilities of this period. We compared adolescent (Postnatal Days 28-42) and adult (Postnatal Day 60+) rats as they performed a simple instrumental task and extinction. Rats were trained to poke into a hole for a food-pellet reinforcer. After six days of training, rats underwent extinction sessions in which the previously rewarded behavior was no longer reinforced. During extinction, we examined the effects of continued presentation of a cue light and food restriction. Adults and adolescents exhibited similar performance during training, although adolescents made more task-irrelevant pokes, consistent with increased exploration. Adults made more premature pokes, which could indicate a more exclusive focus on the task. During extinction, adolescents made more perseverative (previously reinforced) pokes than adults. This behavior was strongly modulated by the combination of motivational factors present (food restriction and cue light), indicating that adolescents were differentially sensitive to them. Furthermore, food restriction induced greater open-field activity in adolescents but not in adults. Thus, as the neural circuitry of motivated behavior develops substantially during adolescence, so too does the behavioral sensitivity to motivational factors. Understanding how such factors differently affect adolescents may shed light on mechanisms that lead to the development of disorders that are manifested during this period.

  14. Activation of the Infralimbic Cortex in a Fear Context Enhances Extinction Learning

    Science.gov (United States)

    Thompson, Brittany M.; Baratta, Michael V.; Biedenkapp, Joseph C.; Rudy, Jerry W.; Watkins, Linda R.; Maier, Steven F.

    2010-01-01

    Activation of the infralimbic region (IL) of the medial prefrontal cortex (mPFC) reduces conditioned fear in a variety of situations, and the IL is thought to play an important role in the extinction of conditioned fear. Here we report a series of experiments using contextual fear conditioning in which the IL is activated with the GABAa antagonist…

  15. Extinction, Spontaneous Recovery and Renewal of Flavor Preferences Based on Taste-Taste Learning

    Science.gov (United States)

    Diaz, Estrella; De la Casa, L. G.

    2011-01-01

    This paper presents evidence of extinction, spontaneous recovery and renewal in a conditioned preferences paradigm based on taste-taste associations. More specifically, in three experiments rats exposed to a simultaneous compound of citric acid-saccharin solution showed a preference for the citric solution when the preference was measured with a…

  16. The Metabotropic Glutamate Receptor, mGlu5, Is Required for Extinction Learning That Occurs in the Absence of a Context Change

    Science.gov (United States)

    André, Marion Agnes Emma; Güntürkün, Onur; Manahan-Vaughan, Denise

    2015-01-01

    The metabotropic glutamate (mGlu) receptors and, in particular, mGlu5 are crucially involved in multiple forms of synaptic plasticity that are believed to underlie explicit memory. MGlu5 is also required for information transfer through neuronal oscillations and for spatial memory. Furthermore, mGlu5 is involved in extinction of implicit forms of learning. This places this receptor in a unique position with regard to information encoding. Here, we explored the role of this receptor in context-dependent extinction learning under constant, or changed, contextual conditions. Animals were trained over 3 days to take a left turn under 25% reward probability in a T-maze with a distinct floor pattern (Context A). On Day 4, they experienced either a floor pattern change (Context B) or the same floor pattern (Context A) in the absence of reward. After acquisition of the task, the animals were returned to the maze once more on Day 5 (Context A, no reward). Treatment with the mGlu5 antagonist, 2-methyl-6-(phenylethynyl) pyridine, before maze exposure on Day 4 completely inhibited extinction learning in the AAA paradigm but had no effect in the ABA paradigm. A subsequent return to the original context (A, on Day 5) revealed successful extinction in the AAA paradigm, but impairment of extinction in the ABA paradigm. These data support that although extinction learning in a new context is unaffected by mGlu5 antagonism, extinction of the consolidated context is impaired. This suggests that mGlu5 is intrinsically involved in enabling learning that once-relevant information is no longer valid. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc. PMID:25160592

  17. The metabotropic glutamate receptor, mGlu5, is required for extinction learning that occurs in the absence of a context change.

    Science.gov (United States)

    André, Marion Agnes Emma; Güntürkün, Onur; Manahan-Vaughan, Denise

    2015-02-01

    The metabotropic glutamate (mGlu) receptors and, in particular, mGlu5 are crucially involved in multiple forms of synaptic plasticity that are believed to underlie explicit memory. MGlu5 is also required for information transfer through neuronal oscillations and for spatial memory. Furthermore, mGlu5 is involved in extinction of implicit forms of learning. This places this receptor in a unique position with regard to information encoding. Here, we explored the role of this receptor in context-dependent extinction learning under constant, or changed, contextual conditions. Animals were trained over 3 days to take a left turn under 25% reward probability in a T-maze with a distinct floor pattern (Context A). On Day 4, they experienced either a floor pattern change (Context B) or the same floor pattern (Context A) in the absence of reward. After acquisition of the task, the animals were returned to the maze once more on Day 5 (Context A, no reward). Treatment with the mGlu5 antagonist, 2-methyl-6-(phenylethynyl) pyridine, before maze exposure on Day 4 completely inhibited extinction learning in the AAA paradigm but had no effect in the ABA paradigm. A subsequent return to the original context (A, on Day 5) revealed successful extinction in the AAA paradigm, but impairment of extinction in the ABA paradigm. These data support that although extinction learning in a new context is unaffected by mGlu5 antagonism, extinction of the consolidated context is impaired. This suggests that mGlu5 is intrinsically involved in enabling learning that once-relevant information is no longer valid.

  18. Adolescent social defeat alters N-methyl-D-aspartic acid receptor expression and impairs fear learning in adulthood.

    Science.gov (United States)

    Novick, Andrew M; Mears, Mackenzie; Forster, Gina L; Lei, Yanlin; Tejani-Butt, Shanaz M; Watt, Michael J

    2016-05-01

    Repeated social defeat of adolescent male rats results in adult mesocortical dopamine hypofunction, impaired working memory, and increased contextual anxiety-like behavior. Given the role of glutamate in dopamine regulation, cognition, and fear and anxiety, we investigated potential changes to N-methyl-D-aspartic acid (NMDA) receptors following adolescent social defeat. As both NMDA receptors and mesocortical dopamine are implicated in the expression and extinction of conditioned fear, a separate cohort of rats was challenged with a classical fear conditioning paradigm to investigate whether fear learning is altered by adolescent defeat. Quantitative autoradiography was used to measure 3H-MK-801 binding to NMDA receptors in regions of the medial prefrontal cortex, caudate putamen, nucleus accumbens, amygdala and hippocampus. Assessment of fear learning was achieved using an auditory fear conditioning paradigm, with freezing toward the auditory tone used as a measure of conditioned fear. Compared to controls, adolescent social defeat decreased adult NMDA receptor expression in the infralimbic region of the prefrontal cortex and central amygdala, while increasing expression in the CA3 region of the hippocampus. Previously defeated rats also displayed decreased conditioned freezing during the recall and first extinction periods, which may be related to the observed decreases and increases in NMDA receptors within the central amygdala and CA3, respectively. The alteration in NMDA receptors seen following adolescent social defeat suggests that dysfunction of glutamatergic systems, combined with mesocortical dopamine deficits, likely plays a role in the some of the long-term behavioral consequences of social stressors in adolescence seen in both preclinical and clinical studies.

  19. Neuronal circuits of fear extinction.

    Science.gov (United States)

    Herry, Cyril; Ferraguti, Francesco; Singewald, Nicolas; Letzkus, Johannes J; Ehrlich, Ingrid; Lüthi, Andreas

    2010-02-01

    Fear extinction is a form of inhibitory learning that allows for the adaptive control of conditioned fear responses. Although fear extinction is an active learning process that eventually leads to the formation of a consolidated extinction memory, it is a fragile behavioural state. Fear responses can recover spontaneously or subsequent to environmental influences, such as context changes or stress. Understanding the neuronal substrates of fear extinction is of tremendous clinical relevance, as extinction is the cornerstone of psychological therapy of several anxiety disorders and because the relapse of maladaptative fear and anxiety is a major clinical problem. Recent research has begun to shed light on the molecular and cellular processes underlying fear extinction. In particular, the acquisition, consolidation and expression of extinction memories are thought to be mediated by highly specific neuronal circuits embedded in a large-scale brain network including the amygdala, prefrontal cortex, hippocampus and brain stem. Moreover, recent findings indicate that the neuronal circuitry of extinction is developmentally regulated. Here, we review emerging concepts of the neuronal circuitry of fear extinction, and highlight novel findings suggesting that the fragile phenomenon of extinction can be converted into a permanent erasure of fear memories. Finally, we discuss how research on genetic animal models of impaired extinction can further our understanding of the molecular and genetic bases of human anxiety disorders.

  20. Social stress reactivity alters reward and punishment learning

    OpenAIRE

    Cavanagh, James F.; Frank, Michael J.; Allen, John J.B.

    2010-01-01

    To examine how stress affects cognitive functioning, individual differences in trait vulnerability (punishment sensitivity) and state reactivity (negative affect) to social evaluative threat were examined during concurrent reinforcement learning. Lower trait-level punishment sensitivity predicted better reward learning and poorer punishment learning; the opposite pattern was found in more punishment sensitive individuals. Increasing state-level negative affect was directly related to punishme...

  1. The role of ventral and dorsal striatum mGluR5 in relapse to cocaine-seeking and extinction learning.

    Science.gov (United States)

    Knackstedt, Lori A; Trantham-Davidson, Heather L; Schwendt, Marek

    2014-01-01

    Cocaine addiction is a chronic, relapsing disease characterized by an inability to regulate drug-seeking behavior. Here we investigated the role of mGluR5 in the ventral and dorsal striatum in regulating cocaine-seeking following both abstinence and extinction. Animals underwent 2 weeks of cocaine self-administration followed by 3 weeks of home-cage abstinence. Animals were then reintroduced to the operant chamber for a context-induced relapse test, followed by 7-10 days of extinction training. Once responding was extinguished, cue-primed reinstatement test was conducted. Both drug-seeking tests were conducted in the presence of either mGluR5 negative allosteric modulator, MTEP or vehicle infused into either the nucleus accumbens (NA) core or dorsolateral striatum (dSTR). We found that MTEP infused in the NA core attenuated both context-induced relapse following abstinence and cue-primed reinstatement following extinction training. Blocking dSTR mGluR5 had no effect on context- or cue-induced cocaine-seeking. However, the intra-dSTR MTEP infusion on the context-induced relapse test day attenuated extinction learning for 4 days after the infusion. Furthermore, mGluR5 surface expression was reduced and LTD was absent in dSTR slices of animals undergoing 3 weeks of abstinence from cocaine but not sucrose self-administration. LTD was restored by bath application of VU-29, a positive allosteric modulator of mGluR5. Bath application of MTEP prevented the induction of LTD in dSTR slices from sucrose animals. Taken together, this data indicates that dSTR mGluR5 plays an essential role in extinction learning but not cocaine relapse, while NA core mGluR5 modulates drug-seeking following both extinction and abstinence from cocaine self-administration.

  2. Microstimulation of the human substantia nigra alters reinforcement learning.

    Science.gov (United States)

    Ramayya, Ashwin G; Misra, Amrit; Baltuch, Gordon H; Kahana, Michael J

    2014-05-14

    Animal studies have shown that substantia nigra (SN) dopaminergic (DA) neurons strengthen action-reward associations during reinforcement learning, but their role in human learning is not known. Here, we applied microstimulation in the SN of 11 patients undergoing deep brain stimulation surgery for the treatment of Parkinson's disease as they performed a two-alternative probability learning task in which rewards were contingent on stimuli, rather than actions. Subjects demonstrated decreased learning from reward trials that were accompanied by phasic SN microstimulation compared with reward trials without stimulation. Subjects who showed large decreases in learning also showed an increased bias toward repeating actions after stimulation trials; therefore, stimulation may have decreased learning by strengthening action-reward associations rather than stimulus-reward associations. Our findings build on previous studies implicating SN DA neurons in preferentially strengthening action-reward associations during reinforcement learning.

  3. Extinction and Latent Inhibition Involve a Similar Form of Inhibitory Learning that is Stored in and Retrieved from the Infralimbic Cortex.

    Science.gov (United States)

    Lingawi, Nura W; Westbrook, R Fredrick; Laurent, Vincent

    2016-10-20

    Extinction and latent inhibition each refer to a reduction in conditioned responding: the former occurs when pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US) are followed by repeated presentations of the CS alone; the latter occurs when CS alone presentations precede its pairings with the US. The present experiments used fear conditioning to test the hypothesis that both phenomena involve a similar form of inhibitory learning that recruits common neuronal substrates. We found that the initial inhibitory memory established by extinction is reactivated in the infralimbic (IL) cortex during additional extinction. Remarkably, this reactivation also occurs when the initial inhibitory memory had been established by latent inhibition. In both cases, the inhibitory memory was strengthened by pharmacological stimulation of the IL. Moreover, NMDA receptor blockade in the IL disrupted the weakening in conditioned responding produced by either latent inhibition or extinction. These findings, therefore, indicate that latent inhibition and extinction produce a similar inhibitory memory that is retrieved from the IL. They also demonstrate that the IL plays a wide role in fear regulation by promoting the retrieval of inhibitory memories generated by CS alone presentations either before or after this CS has been rendered dangerous.

  4. Beta-adrenergic receptors support attention to extinction learning that occurs in the absence, but not the presence, of a context change

    Directory of Open Access Journals (Sweden)

    Marion Emma André

    2015-05-01

    Full Text Available The noradrenergic (NA-system is an important regulator of cognitive function. It contributes to extinction learning(EL, and in disorders where EL is impaired NA-dysfunction has been postulated. We explored whether NA acting on beta-adrenergic-receptors (β-AR, regulates EL that depends on context, but is not fear-associated. We assessed behaviour in an ‘AAA’ or ‘ABA’ paradigm: rats were trained for 3 days in a T-maze(context-A to learn that a reward is consistently found in the goal arm, despite low reward probability. This was followed on day 4 by EL(unrewarded, whereby in the ABA-paradigm, EL was reinforced by a context change (B, and in the AAA-paradigm, no context change occurred. On day 5, re-exposure to the A-context (unrewarded occurred. Typically, in control ‘AAA’ animals EL occurred on day 4 that progressed further on day 5. In control ‘ABA’ animals, EL also occurred on day 4, followed by renewal of the previously learned (A behavior on day 5, that was followed (in day 5 by extinction of this behavior, as the animals realised that no food reward would be given.Treatment with the β-AR-antagonist, propranolol, prior to EL on day 4, impaired EL in the AAA-paradigm. In the ‘ABA’ paradigm, antagonist treatment on day 4, had no effect on extinction that was reinforced by a context change (B. Furthermore, β-AR-antagonism prior to renewal testing (on day 5 in the ABA-paradigm, resulted in normal renewal behavior, although subsequent extinction of responses during day 5 was prevented by the antagonist. Thus, under both treatment conditions, β-AR-antagonism prevented extinction of the behavior learned in the ‘A’ context.β-AR-blockade during an overt context change did not prevent EL, whereas β-AR were required for EL in an unchanging context. These data suggest that β-AR may support EL by reinforcing attention towards relevant changes in the previously learned experience, and that this process supports extinction

  5. Beta-adrenergic receptors support attention to extinction learning that occurs in the absence, but not the presence, of a context change

    Science.gov (United States)

    André, Marion Agnès Emma; Wolf, Oliver T.; Manahan-Vaughan, Denise

    2015-01-01

    The noradrenergic (NA)-system is an important regulator of cognitive function. It contributes to extinction learning (EL), and in disorders where EL is impaired NA-dysfunction has been postulated. We explored whether NA acting on beta-adrenergic-receptors (β-AR), regulates EL that depends on context, but is not fear-associated. We assessed behavior in an “AAA” or “ABA” paradigm: rats were trained for 3 days in a T-maze (context-A) to learn that a reward is consistently found in the goal arm, despite low reward probability. This was followed on day 4 by EL (unrewarded), whereby in the ABA-paradigm, EL was reinforced by a context change (B), and in the AAA-paradigm, no context change occurred. On day 5, re-exposure to the A-context (unrewarded) occurred. Typically, in control “AAA” animals EL occurred on day 4 that progressed further on day 5. In control “ABA” animals, EL also occurred on day 4, followed by renewal of the previously learned (A) behavior on day 5, that was succeeded (on day 5) by extinction of this behavior, as the animals realised that no food reward would be given. Treatment with the β-AR-antagonist, propranolol, prior to EL on day 4, impaired EL in the AAA-paradigm. In the “ABA” paradigm, antagonist treatment on day 4, had no effect on extinction that was reinforced by a context change (B). Furthermore, β-AR-antagonism prior to renewal testing (on day 5) in the ABA-paradigm, resulted in normal renewal behavior, although subsequent extinction of responses during day 5 was prevented by the antagonist. Thus, under both treatment conditions, β-AR-antagonism prevented extinction of the behavior learned in the “A” context. β-AR-blockade during an overt context change did not prevent EL, whereas β-AR were required for EL in an unchanging context. These data suggest that β-AR may support EL by reinforcing attention towards relevant changes in the previously learned experience, and that this process supports extinction

  6. Genetic Inactivation of D-Amino Acid Oxidase Enhances Extinction and Reversal Learning in Mice

    Science.gov (United States)

    Labrie, Viviane; Duffy, Steven; Wang, Wei; Barger, Steven W.; Baker, Glen B.; Roder, John C.

    2009-01-01

    Activation of the N-methyl-d-aspartate receptor (NMDAR) glycine site has been shown to accelerate adaptive forms of learning that may benefit psychopathologies involving cognitive and perseverative disturbances. In this study, the effects of increasing the brain levels of the endogenous NMDAR glycine site agonist D-serine, through the genetic…

  7. Zinc Transporter 3 Is Involved in Learned Fear and Extinction, but Not in Innate Fear

    Science.gov (United States)

    Martel, Guillaume; Hevi, Charles; Friebely, Olivia; Baybutt, Trevor; Shumyatsky, Gleb P.

    2010-01-01

    Synaptically released Zn[superscript 2+] is a potential modulator of neurotransmission and synaptic plasticity in fear-conditioning pathways. Zinc transporter 3 (ZnT3) knock-out (KO) mice are well suited to test the role of zinc in learned fear, because ZnT3 is colocalized with synaptic zinc, responsible for its transport to synaptic vesicles,…

  8. Alterity: Learning Polyvalent Selves, Resisting Disabling Notions of the Self

    Science.gov (United States)

    Walker, Wayland

    2011-01-01

    This article queries how one type of human difference--alterity, the experience of multiple distinct consciousnesses, or "alters," by one person--is pathologized in American culture. This experience is inscribed as a mental illness, labeled now as dissociative identity disorder (DID) and formerly known as multiple personality disorder (MPD). In…

  9. Effects of neonatal amygdala lesions on fear learning, conditioned inhibition, and extinction in adult macaques.

    Science.gov (United States)

    Kazama, Andy M; Heuer, Eric; Davis, Michael; Bachevalier, Jocelyne

    2012-06-01

    Fear conditioning studies have demonstrated the critical role played by the amygdala in emotion processing. Although all lesion studies until now investigated the effect of adult-onset damage on fear conditioning, the current study assessed fear-learning abilities, as measured by fear-potentiated startle, in adult monkeys that had received neonatal neurotoxic amygdala damage or sham-operations. After fear acquisition, their abilities to learn and use a safety cue to modulate their fear to the conditioned cue, and, finally, to extinguish their response to the fear conditioned cue were measured with the AX+/BX- Paradigm. Neonatal amygdala damage retarded, but did not completely abolish, the acquisition of a learned fear. After acquisition of the fear signal, four of the six animals with neonatal amygdala lesions discriminated between the fear and safety cues and were also able to use the safety signal to reduce the potentiated-startle response and to extinguish the fear response when the air-blast was absent. In conclusion, the present results support the critical contribution of the amygdala during the early phases of fear conditioning that leads to quick, robust responses to potentially threatening stimuli, a highly adaptive process across all species and likely to be present in early infancy. The neonatal amygdala lesions also indicated the presence of amygdala-independent alternate pathways that are capable to support fear learning in the absence of a functional amygdala. This parallel processing of fear responses within these alternate pathways was also sufficient to support the ability to flexibly modulate the magnitude of the fear responses.

  10. Learning arm/hand coordination with an altered visual input.

    Science.gov (United States)

    Iftime Nielsen, Simona Denisia; Dosen, Strahinja; Popović, Mirjana B; Popović, Dejan B

    2010-01-01

    The focus of this study was to test a novel tool for the analysis of motor coordination with an altered visual input. The altered visual input was created using special glasses that presented the view as recorded by a video camera placed at various positions around the subject. The camera was positioned at a frontal (F), lateral (L), or top (T) position with respect to the subject. We studied the differences between the arm-end (wrist) trajectories while grasping an object between altered vision (F, L, and T conditions) and normal vision (N) in ten subjects. The outcome measures from the analysis were the trajectory errors, the movement parameters, and the time of execution. We found substantial trajectory errors and an increased execution time at the baseline of the study. We also found that trajectory errors decreased in all conditions after three days of practice with the altered vision in the F condition only for 20 minutes per day, suggesting that recalibration of the visual systems occurred relatively quickly. These results indicate that this recalibration occurs via movement training in an altered condition. The results also suggest that recalibration is more difficult to achieve for altered vision in the F and L conditions compared to the T condition. This study has direct implications on the design of new rehabilitation systems.

  11. Behavioral and neurophysiological evidence that lateral paracapsular GABAergic synapses in the basolateral amygdala contribute to the acquisition and extinction of fear learning.

    Science.gov (United States)

    Skelly, M J; Chappell, A M; Ariwodola, O J; Weiner, J L

    2016-01-01

    The lateral/basolateral amygdala (BLA) is crucial to the acquisition and extinction of Pavlovian fear conditioning, and synaptic plasticity in this region is considered to be a neural correlate of learned fear. We recently reported that activation of BLA β3-adrenoreceptors (β3-ARs) selectively enhances lateral paracapsular (LPC) feed-forward GABAergic inhibition onto BLA pyramidal neurons, and that intra-BLA infusion of a β3-AR agonist reduces measures of unconditioned anxiety-like behavior. Here, we utilized a combination of behavioral and electrophysiological approaches to characterize the role of BLA LPCs in the acquisition of fear and extinction learning in adult male Long-Evans rats. We report that intra-BLA microinjection of β3-AR agonists (BRL37344 or SR58611A, 1μg/0.5μL/side) prior to training fear conditioning or extinction blocks the expression of these behaviors 24h later. Furthermore,ex vivo low-frequency stimulation of the external capsule (LFS; 1Hz, 15min), which engages LPC synapses, induces LTP of BLA fEPSPs, while application of a β3-AR agonist (SR58611A, 5μM) induces LTD of fEPSPs when combined with LFS. Interestingly, fEPSP LTP is not observed in recordings from fear conditioned animals, suggesting that fear learning may engage the same mechanisms that induce synaptic plasticity at this input. In support of this, we find that LFS produces LTD of inhibitory postsynaptic currents (iLTD) at LPC GABAergic synapses, and that this effect is also absent following fear conditioning. Taken together, these data provide preliminary evidence that modulation of LPC GABAergic synapses can influence the acquisition and extinction of fear learning and related synaptic plasticity in the BLA.

  12. Brain and behavioral evidence for altered social learning mechanisms among women with assault-related posttraumatic stress disorder.

    Science.gov (United States)

    Cisler, Josh M; Bush, Keith; Scott Steele, J; Lenow, Jennifer K; Smitherman, Sonet; Kilts, Clinton D

    2015-04-01

    Current neurocircuitry models of PTSD focus on the neural mechanisms that mediate hypervigilance for threat and fear inhibition/extinction learning. Less focus has been directed towards explaining social deficits and heightened risk of revictimization observed among individuals with PTSD related to physical or sexual assault. The purpose of the present study was to foster more comprehensive theoretical models of PTSD by testing the hypothesis that assault-related PTSD is associated with behavioral impairments in a social trust and reciprocity task and corresponding alterations in the neural encoding of social learning mechanisms. Adult women with assault-related PTSD (n = 25) and control women (n = 15) completed a multi-trial trust game outside of the MRI scanner. A subset of these participants (15 with PTSD and 14 controls) also completed a social and non-social reinforcement learning task during 3T fMRI. Brain regions that encoded the computationally modeled parameters of value expectation, prediction error, and volatility (i.e., uncertainty) were defined and compared between groups. The PTSD group demonstrated slower learning rates during the trust game and social prediction errors had a lesser impact on subsequent investment decisions. PTSD was also associated with greater encoding of negative expected social outcomes in perigenual anterior cingulate cortex and bilateral middle frontal gyri, and greater encoding of social prediction errors in the left temporoparietal junction. These data suggest mechanisms of PTSD-related deficits in social functioning and heightened risk for re-victimization in assault victims; however, comorbidity in the PTSD group and the lack of a trauma-exposed control group temper conclusions about PTSD specifically.

  13. Biologically based neural circuit modelling for the study of fear learning and extinction

    Science.gov (United States)

    Nair, Satish S.; Paré, Denis; Vicentic, Aleksandra

    2016-11-01

    The neuronal systems that promote protective defensive behaviours have been studied extensively using Pavlovian conditioning. In this paradigm, an initially neutral-conditioned stimulus is paired with an aversive unconditioned stimulus leading the subjects to display behavioural signs of fear. Decades of research into the neural bases of this simple behavioural paradigm uncovered that the amygdala, a complex structure comprised of several interconnected nuclei, is an essential part of the neural circuits required for the acquisition, consolidation and expression of fear memory. However, emerging evidence from the confluence of electrophysiological, tract tracing, imaging, molecular, optogenetic and chemogenetic methodologies, reveals that fear learning is mediated by multiple connections between several amygdala nuclei and their distributed targets, dynamical changes in plasticity in local circuit elements as well as neuromodulatory mechanisms that promote synaptic plasticity. To uncover these complex relations and analyse multi-modal data sets acquired from these studies, we argue that biologically realistic computational modelling, in conjunction with experiments, offers an opportunity to advance our understanding of the neural circuit mechanisms of fear learning and to address how their dysfunction may lead to maladaptive fear responses in mental disorders.

  14. Reproductive experience does not persistently alter prefrontal cortical-dependent learning but does alter strategy use dependent on estrous phase.

    Science.gov (United States)

    Workman, Joanna L; Crozier, Tamara; Lieblich, Stephanie E; Galea, Liisa A M

    2013-08-01

    Reproductive experiences in females comprise substantial hormonal and experiential changes and can exert long lasting changes in cognitive function, stress physiology, and brain plasticity. The goal of this research was to determine whether prior reproductive experience could alter a prefrontal-cortical dependent form of learning (strategy set shifting) in an operant box. In this study, female Sprague-Dawley rats were mated and mothered once or twice to produce either primiparous or biparous dams, respectively. Age-matched nulliparous controls (reproductively-naïve females with no exposure to pup cues) were also used. Maternal behaviors were also assessed to determine whether these factors would predict cognitive flexibility. For strategy set shifting, rats were trained in a visual-cue discrimination task on the first day and on the following day, were required to switch to a response strategy to obtain a reward. We also investigated a simpler form of behavioral flexibility (reversal learning) in which rats were trained to press a lever on one side of the box the first day, and on the following day, were required to press the opposite lever to obtain a reward. Estrous phase was determined daily after testing. Neither parity nor estrous phase altered total errors or trials to reach criterion in either the set-shifting or reversal-learning tasks, suggesting that PFC-dependent cognitive performance remains largely stable after 1 or 2 reproductive experiences. However, parity and estrous phase interacted to alter the frequency of particular error types, with biparous rats in estrus committing more perseverative but fewer regressive errors during the set-shifting task. This suggests that parity and estrous phase interfere with the ability to disengage from a previously used, but no longer relevant strategy. These data also suggest that parity alters the behavioral sensitivity to ovarian hormones without changing overall performance.

  15. The type 3 adenylyl cyclase is required for novel object learning and extinction of contextual memory: role of cAMP signaling in primary cilia.

    Science.gov (United States)

    Wang, Zhenshan; Phan, Trongha; Storm, Daniel R

    2011-04-13

    Although primary cilia are found on neurons throughout the brain, their physiological function remains elusive. Human ciliopathies are associated with cognition defects, and transgenic mice lacking proteins expressed in primary cilia exhibit defects in learning and memory. Recently, it was reported that mice lacking the G-protein-coupling receptor somatostatin receptor-3 (SSTR3), a protein expressed predominately in the primary cilia of neurons, have defective memory for novel object recognition and lower cAMP levels in the brain. Since SSTR3 is coupled to regulation of adenylyl cyclase, this suggests that adenylyl cyclase activity in primary cilia of CNS neurons may be critical for some forms of learning and memory. Because the type 3 adenylyl cyclase (AC3) is expressed in primary cilia of hippocampal neurons, we examined AC3(-/-) mice for several forms of learning and memory. Here, we report that AC3(-/-) mice show no short-term memory for novel objects and fail to exhibit extinction of contextual fear conditioning. They also show impaired learning and memory for temporally dissociative passive avoidance. Since AC3 is exclusively expressed in primary cilia, we conclude that cAMP signals generated within primary cilia contribute to some forms of learning and memory, including extinction of contextual fear conditioning.

  16. Altered motivation masks appetitive learning potential of obese mice

    Directory of Open Access Journals (Sweden)

    Mazen R. Harb

    2014-10-01

    Full Text Available Eating depends strongly on learning processes which, in turn, depend on motivation. Conditioned learning, where individuals associate environmental cues with receipt of a reward, forms an important part of hedonic mechanisms; the latter contribute to the development of human overweight and obesity by driving excessive eating in what may become a vicious cycle. Although mice are commonly used to explore the regulation of human appetite, it is not known whether their conditioned learning of food rewards varies as a function of body mass. To address this, groups of adult male mice of differing body weights were tested two appetitive conditioning paradigms (pavlovian and operant as well as in food retrieval and hedonic preference tests in an attempt to dissect the respective roles of learning/motivation and energy state in the regulation of feeding behavior. We found that i the rate of pavlovian conditioning to an appetitive reward develops as an inverse function of body weight; ii higher body weight associates with increased latency to collect food reward; and iii mice with lower body weights are more motivated to work for a food reward, as compared to animals with higher body weights. Interestingly, as compared to controls, overweight and obese mice consumed smaller amounts of palatable foods (isocaloric milk or sucrose, in either the presence or absence of their respective maintenance diets: standard, low fat-high carbohydrate or high fat-high carbohydrate. Notably, however, all groups adjusted their consumption of the different food types, such that their body weight-corrected daily intake of calories remained constant. Thus, overeating in mice does not reflect a reward deficiency syndrome and, in contrast to humans, mice regulate their caloric intake according to metabolic status rather than to the hedonic properties of a particular food. Together, these observations demonstrate that excess weight masks the capacity for appetitive learning in

  17. The roles of the nucleus accumbens core, dorsomedial striatum, and dorsolateral striatum in learning: performance and extinction of Pavlovian fear-conditioned responses and instrumental avoidance responses.

    Science.gov (United States)

    Wendler, Etieli; Gaspar, Jessica C C; Ferreira, Tatiana L; Barbiero, Janaína K; Andreatini, Roberto; Vital, Maria A B F; Blaha, Charles D; Winn, Philip; Da Cunha, Claudio

    2014-03-01

    This study examined the effects of bilateral excitotoxic lesions of the nucleus accumbens core (NAc-co), dorsomedial striatum (DMS) or dorsolateral striatum (DLS) of rats on the learning and extinction of Pavlovian and instrumental components of conditioned avoidance responses (CARs). None of the lesions caused sensorimotor deficits that could affect locomotion. Lesions of the NAc-co, but not DMS or DLS, decreased unconditioned and conditioned freezing. The NAc-co and DLS lesioned rats learned the 2-way active avoidance task more slowly. These results suggest: (i) CARs depend on both Pavlovian and instrumental learning; (ii) learning the Pavlovian component of CARs depends on the NAc-co; learning the instrumental component of CARs depends on the DLS, NAc and DMS; (iii) although the NAc-co is also needed for learning the instrumental component, it is not clear whether it plays a role in learning the instrumental component per se or if it simply allows learning of the Pavlovian component which is a pre-condition for learning the instrumental component; (iv) we did not find evidence that the DMS and DLS play the same roles in habit and goal-directed aspects of the instrumental component of CARs as observed in appetitive motivated instrumental responding.

  18. [Neurobiology of learning--the basis of an alteration process].

    Science.gov (United States)

    Braus, Dieter F

    2004-11-01

    In contrast to the opinion that prevailed in the 1980es, there is now increasing evidence that the plasticity of the human brain, i. e. its remarkable ability to adapt to and change with experience, is, under normal conditions, a lifelong phenomenon. Representations of the environment are associated with activations and biochemical modifications in neuronal networks, which will be stabilized, modified or will wither in the course of cumulated experience. The capability to modify the biochemistry of synapses as well as the growth and change in terms of rewiring of synapses, dendritic branching and glial cell proliferation via the dialogue of synapses and genes, results in specific changes in neuronal connectivity and function. On the neurotransmitter level, glutamate and gamma-amino-butyric acid (GABA) as well as dopamine and serotonin, but also endorphin and encephalin, have a key position in this context. These neurotransmitter systems modulate neuronal plasticity on the neuronal level; on the behavioural level they influence affect, emotion, positive motivation and the correct evaluation of environmental stimuli. Experience, action as well as learning and memory are influenced by these systems. A basic thesis of this paper is that these mechanisms are involved in neuronal plasticity and that learning and memory are thus not only used and reused in structuring the CNS during the initial establishment of connections in the immature brain, in lifelong memory consolidation or the rewiring after brain damage, but can also be used to mould experience, learning und behaviour during psychotherapy and rehabilitation in adults.

  19. Stress during puberty boosts metabolic activation associated with fear-extinction learning in hippocampus, basal amygdala and cingulate cortex.

    Science.gov (United States)

    Toledo-Rodriguez, Maria; Pitiot, Alain; Paus, Tomáš; Sandi, Carmen

    2012-07-01

    Adolescence is characterized by major developmental changes that may render the individual vulnerable to stress and the development of psychopathologies in a sex-specific manner. Earlier we reported lower anxiety-like behavior and higher risk-taking and novelty seeking in rats previously exposed to peri-pubertal stress. Here we studied whether peri-pubertal stress affected the acquisition and extinction of fear memories and/or the associated functional engagement of various brain regions, as assessed with 2-deoxyglucose. We showed that while peri-pubertal stress reduced freezing during the acquisition of fear memories (training) in both sexes, it had a sex-specific effect on extinction of these memories. Moreover hippocampus, basal amygdala and cingulate and motor cortices showed higher metabolic rates during extinction in rats exposed to peri-pubertal stress. Interestingly, activation of the infralimbic cortex was negatively correlated with freezing during extinction only in control males, while only males stressed during puberty showed a significant correlation between behavior during extinction and metabolic activation of hippocampus, amygdala and paraventricular nucleus. No correlations between brain activation and behavior during extinction were observed in females (control or stress). These results indicate that exposure to peri-pubertal stress affects behavior and brain metabolism when the individual is exposed to an additional stressful challenge. Some of these effects are sex-specific.

  20. FKBP5 polymorphisms influence pre-learning stress-induced alterations of learning and memory.

    Science.gov (United States)

    Zoladz, Phillip R; Dailey, Alison M; Nagle, Hannah E; Fiely, Miranda K; Mosley, Brianne E; Brown, Callie M; Duffy, Tessa J; Scharf, Amanda R; Earley, McKenna B; Rorabaugh, Boyd R

    2017-03-01

    FK506 binding protein 51 (FKBP5) is a co-chaperone of heat shock protein 90 and significantly influences glucocorticoid receptor sensitivity. Single nucleotide polymorphisms (SNPs) in the FKBP5 gene are associated with altered hypothalamus-pituitary-adrenal (HPA) axis function, changes in the structure and function of several cognitive brain areas, and increased susceptibility to post-traumatic stress disorder, major depression, bipolar disorder and suicidal events. The mechanisms underlying these associations are largely unknown, but it has been speculated that the influence of these SNPs on emotional memory systems may play a role. In the present study, 112 participants were exposed to the socially evaluated cold pressor test (stress) or control (no stress) conditions immediately prior to learning a list of 42 words. Participant memory was assessed immediately after learning (free recall) and 24 h later (free recall and recognition). Participants provided a saliva sample that enabled the genotyping of three FKBP5 polymorphisms: rs1360780, rs3800373 and rs9296158. Results showed that stress impaired immediate recall in risk allele carriers. More importantly, stress enhanced long-term recall and recognition memory in non-carriers of the risk alleles, effects that were completely absent in risk allele carriers. Follow-up analyses revealed that memory performance was correlated with salivary cortisol levels in non-carriers, but not in carriers. These findings suggest that FKBP5 risk allele carriers may possess a sensitized stress response system, perhaps specifically for stress-induced changes in corticosteroid levels, which might aid our understanding of how SNPs in the FKBP5 gene confer increased risk for stress-related psychological disorders and their related phenotypes.

  1. Immediate extinction causes a less durable loss of performance than delayed extinction following either fear or appetitive conditioning

    OpenAIRE

    Woods, Amanda M.; Bouton, Mark E.

    2008-01-01

    Five experiments with rat subjects compared the effects of immediate and delayed extinction on the durability of extinction learning. Three experiments examined extinction of fear conditioning (using the conditioned emotional response method), and two experiments examined extinction of appetitive conditioning (using the food-cup entry method). In all experiments, conditioning and extinction were accomplished in single sessions, and retention testing took place 24 h after extinction. In both f...

  2. Effects of rapid eye movement sleep deprivation on fear extinction recall and prediction error signaling.

    Science.gov (United States)

    Spoormaker, Victor I; Schröter, Manuel S; Andrade, Kátia C; Dresler, Martin; Kiem, Sara A; Goya-Maldonado, Roberto; Wetter, Thomas C; Holsboer, Florian; Sämann, Philipp G; Czisch, Michael

    2012-10-01

    In a temporal difference learning approach of classical conditioning, a theoretical error signal shifts from outcome deliverance to the onset of the conditioned stimulus. Omission of an expected outcome results in a negative prediction error signal, which is the initial step towards successful extinction and may therefore be relevant for fear extinction recall. As studies in rodents have observed a bidirectional relationship between fear extinction and rapid eye movement (REM) sleep, we aimed to test the hypothesis that REM sleep deprivation impairs recall of fear extinction through prediction error signaling in humans. In a three-day design with polysomnographically controlled REM sleep deprivation, 18 young, healthy subjects performed a fear conditioning, extinction and recall of extinction task with visual stimuli, and mild electrical shocks during combined functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) measurements. Compared to the control group, the REM sleep deprivation group had increased SCR scores to a previously extinguished stimulus at early recall of extinction trials, which was associated with an altered fMRI time-course in the left middle temporal gyrus. Post-hoc contrasts corrected for measures of NREM sleep variability also revealed between-group differences primarily in the temporal lobe. Our results demonstrate altered prediction error signaling during recall of fear extinction after REM sleep deprivation, which may further our understanding of anxiety disorders in which disturbed sleep and impaired fear extinction learning coincide. Moreover, our findings are indicative of REM sleep related plasticity in regions that also show an increase in activity during REM sleep.

  3. Role of Dopamine 2 Receptor in Impaired Drug-Cue Extinction in Adolescent Rats.

    Science.gov (United States)

    Zbukvic, Isabel C; Ganella, Despina E; Perry, Christina J; Madsen, Heather B; Bye, Christopher R; Lawrence, Andrew J; Kim, Jee Hyun

    2016-06-01

    Adolescent drug users display resistance to treatment such as cue exposure therapy (CET), as well as increased liability to relapse. The basis of CET is extinction learning, which involves dopamine signaling in the medial prefrontal cortex (mPFC). This system undergoes dramatic alterations during adolescence. Therefore, we investigated extinction of a cocaine-associated cue in adolescent and adult rats. While cocaine self-administration and lever-alone extinction were not different between the two ages, we observed that cue extinction reduced cue-induced reinstatement in adult but not adolescent rats. Infusion of the selective dopamine 2 receptor (D2R)-like agonist quinpirole into the infralimbic cortex (IL) of the mPFC prior to cue extinction significantly reduced cue-induced reinstatement in adolescents. This effect was replicated by acute systemic treatment with the atypical antipsychotic aripiprazole (Abilify), a partial D2R-like agonist. These data suggest that adolescents may be more susceptible to relapse due to a deficit in cue extinction learning, and highlight the significance of D2R signaling in the IL for cue extinction during adolescence. These findings inspire new tactics for improving adolescent CET, with aripiprazole representing an exciting potential pharmacological adjunct for behavioral therapy.

  4. Immediate Extinction Causes a Less Durable Loss of Performance than Delayed Extinction following Either Fear or Appetitive Conditioning

    Science.gov (United States)

    Woods, Amanda M.; Bouton, Mark E.

    2008-01-01

    Five experiments with rat subjects compared the effects of immediate and delayed extinction on the durability of extinction learning. Three experiments examined extinction of fear conditioning (using the conditioned emotional response method), and two experiments examined extinction of appetitive conditioning (using the food-cup entry method). In…

  5. Learning by Living: Life-Altering Medical Education through Nursing Home-Based Experiential Learning

    Science.gov (United States)

    Gugliucci, Marilyn R.; Weiner, Audrey

    2013-01-01

    The University of New England College of Osteopathic Medicine Learning by Living Project (referred to as Learning by Living) was piloted in 2006 as an experiential medical education learning model. Since its inception, medical and other health professions students have been "admitted" into nursing homes to live the life of an older adult nursing…

  6. Serotonin transporter polyadenylation polymorphism modulates the retention of fear extinction memory.

    Science.gov (United States)

    Hartley, Catherine A; McKenna, Morgan C; Salman, Rabia; Holmes, Andrew; Casey, B J; Phelps, Elizabeth A; Glatt, Charles E

    2012-04-01

    Growing evidence suggests serotonin's role in anxiety and depression is mediated by its effects on learned fear associations. Pharmacological and genetic manipulations of serotonin signaling in mice alter the retention of fear extinction learning, which is inversely associated with anxious temperament in mice and humans. Here, we test whether genetic variation in serotonin signaling in the form of a common human serotonin transporter polyadenylation polymorphism (STPP/rs3813034) is associated with spontaneous fear recovery after extinction. We show that the risk allele of this polymorphism is associated with impaired retention of fear extinction memory and heightened anxiety and depressive symptoms. These STPP associations in humans mirror the phenotypic effects of serotonin transporter knockout in mice, highlighting the STPP as a potential genetic locus underlying interindividual differences in serotonin transporter function in humans. Furthermore, we show that the serotonin transporter polyadenylation profile associated with the STPP risk allele is altered through the chronic administration of fluoxetine, a treatment that also facilitates retention of extinction learning. The propensity to form persistent fear associations due to poor extinction recall may be an intermediate phenotype mediating the effects of genetic variation in serotonergic function on anxiety and depression. The consistency and specificity of these data across species provide robust support for this hypothesis and suggest that the little-studied STPP may be an important risk factor for mood and anxiety disorders in humans.

  7. Psychological and neural mechanisms of experimental extinction: a selective review.

    Science.gov (United States)

    Delamater, Andrew R; Westbrook, R Frederick

    2014-02-01

    The present review examines key psychological concepts in the study of experimental extinction and implications these have for an understanding of the underlying neurobiology of extinction learning. We suggest that many of the signature characteristics of extinction learning (spontaneous recovery, renewal, reinstatement, rapid reacquisition) can be accommodated by the standard associative learning theory assumption that extinction results in partial erasure of the original learning together with new inhibitory learning. Moreover, we consider recent behavioral and neural evidence that supports the partial erasure view of extinction, but also note shortcomings in our understanding of extinction circuits as these relate to the negative prediction error concept. Recent work suggests that common prediction error and stimulus-specific prediction error terms both may be required to explain neural plasticity both in acquisition and extinction learning. In addition, we suggest that many issues in the content of extinction learning have not been fully addressed in current research, but that neurobiological approaches should be especially helpful in addressing such issues. These include questions about the nature of extinction learning (excitatory CS-No US, inhibitory CS-US learning, occasion setting processes), especially as this relates to studies of the micro-circuitry of extinction, as well as its representational content (sensory, motivational, response). An additional understudied problem in extinction research is the role played by attention processes and their underlying neural networks, although some research and theory converge on the idea that extinction is accompanied by attention decrements (i.e., habituation-like processes).

  8. The effect of electroacupuncture on extinction responding of heroin-seeking behavior and FosB expression in the nucleus accumbens core.

    Science.gov (United States)

    Hu, Airong; Lai, Miaojun; Wei, Jianzi; Wang, Lina; Mao, Huijuan; Zhou, Wenhua; Liu, Sheng

    2013-02-08

    Augmentation of extinction with learning enhancing therapy may offer an effective strategy to combat heroin relapse. Our lab previously found that electroacupuncture (EA) not only significantly reduced cue-induced reinstatement of heroin seeking but also exhibited a promoting effect on the ability of learning and memory. In the present study, we further investigated the effects of EA on the extinction of heroin-seeking behavior in rats with a history of intravenous heroin self-administration. We trained Sprague-Dawley rats to nose-poke for i.v. heroin either daily for 4h or 25 infusions for 14 consecutive days; then the rats underwent 7 daily 3h extinction sessions in the operant chamber. To assess EA's effects on the extinction response of heroin-associated cues, 2Hz EA was administered 1h before each of the 7 extinction sessions. We also applied immunohistochemistry to detect FosB-positive nuclei in the nucleus accumbens core. We found that EA treatment facilitated the extinction response of heroin seeking but did not alter the locomotor activity in an open field testing environment. EA stimulation attenuated the FosB expression in the core of the nucleus accumbens, a brain region involved in the learning and execution of motor responses. Altogether, these results suggest that EA may provide a novel nonpharmacological approach to enhance extinction learning when combined with extinction therapy for the treatment of heroin addiction.

  9. Impaired extinction of fear conditioning after REM deprivation is magnified by rearing in an enriched environment.

    Science.gov (United States)

    Hunter, Amy Silvestri

    2015-07-01

    Evidence from both human and animal studies indicates that rapid eye movement sleep (REM) is essential for the acquisition and retention of information, particularly of an emotional nature. Learning and memory can also be impacted by manipulation of housing condition such as exposure to an enriched environment (EE). This study investigated the effects of REM deprivation and EE, both separately and combined, on the extinction of conditioned fear in rats. Consistent with prior studies, conditioning was enhanced in EE-reared rats and extinction was impaired in REM deprived rats. In addition, rats exposed to both REM deprivation and EE showed the greatest impairment in extinction, with effects persisting through the first two days of extinction training. This study is the first to explore the combination of REM deprivation and EE and suggests that manipulations that alter sleep, particularly REM, can have persisting deleterious effects on emotional memory processing.

  10. Genetic gating of human fear learning and extinction: possible implications for gene-environment interaction in anxiety disorder.

    Science.gov (United States)

    Lonsdorf, Tina B; Weike, Almut I; Nikamo, Pernilla; Schalling, Martin; Hamm, Alfons O; Ohman, Arne

    2009-02-01

    Pavlovian fear conditioning is a widely used model of the acquisition and extinction of fear. Neural findings suggest that the amygdala is the core structure for fear acquisition, whereas prefrontal cortical areas are given pivotal roles in fear extinction. Forty-eight volunteers participated in a fear-conditioning experiment, which used fear potentiation of the startle reflex as the primary measure to investigate the effect of two genetic polymorphisms (5-HTTLPR and COMTval158met) on conditioning and extinction of fear. The 5-HTTLPR polymorphism, located in the serotonin transporter gene, is associated with amygdala reactivity and neuroticism, whereas the COMTval158met polymorphism, which is located in the gene coding for catechol-O-methyltransferase (COMT), a dopamine-degrading enzyme, affects prefrontal executive functions. Our results show that only carriers of the 5-HTTLPR s allele exhibited conditioned startle potentiation, whereas carriers of the COMT met/met genotype failed to extinguish conditioned fear. These results may have interesting implications for understanding gene-environment interactions in the development and treatment of anxiety disorders.

  11. In the laboratory and during free-flight: old honey bees reveal learning and extinction deficits that mirror mammalian functional decline.

    Directory of Open Access Journals (Sweden)

    Daniel Münch

    Full Text Available Loss of brain function is one of the most negative and feared aspects of aging. Studies of invertebrates have taught us much about the physiology of aging and how this progression may be slowed. Yet, how aging affects complex brain functions, e.g., the ability to acquire new memory when previous experience is no longer valid, is an almost exclusive question of studies in humans and mammalian models. In these systems, age related cognitive disorders are assessed through composite paradigms that test different performance tasks in the same individual. Such studies could demonstrate that afflicted individuals show the loss of several and often-diverse memory faculties, and that performance usually varies more between aged individuals, as compared to conspecifics from younger groups. No comparable composite surveying approaches are established yet for invertebrate models in aging research. Here we test whether an insect can share patterns of decline similar to those that are commonly observed during mammalian brain aging. Using honey bees, we combine restrained learning with free-flight assays. We demonstrate that reduced olfactory learning performance correlates with a reduced ability to extinguish the spatial memory of an abandoned nest location (spatial memory extinction. Adding to this, we show that learning performance is more variable in old honey bees. Taken together, our findings point to generic features of brain aging and provide the prerequisites to model individual aspects of learning dysfunction with insect models.

  12. Learning alters theta amplitude, theta-gamma coupling and neuronal synchronization in inferotemporal cortex

    Directory of Open Access Journals (Sweden)

    Nicol Alister U

    2011-06-01

    which are correlated with behavioral performance. A network model which can reproduce these changes suggests that a key function of such learning-evoked alterations in theta and theta-nested gamma activity may be increased temporal desynchronization in neuronal firing leading to optimal timing of inputs to downstream neural networks potentiating their responses. In this way learning can produce potentiation in neural networks simply through altering the temporal pattern of their inputs.

  13. Outcome-Specific Transfer between Predictive and Instrumental Learning Is Unaffected by Extinction but Reversed by Counterconditioning in Human Participants

    Science.gov (United States)

    Rosas, Juan M.; Paredes-Olay, Maria C.; Garcia-Gutierrez, Ana; Espinosa, Juan J.; Abad, Maria J. F.

    2010-01-01

    Three experiments were conducted to explore the effects of different interference treatments upon outcome-specific transfer from predictive learning to instrumental responding. A computer game was designed in which participants had to defend Andalusia from navy and air-force attacks. Participants learned the relationship between two instrumental…

  14. Role of the hippocampus in contextual modulation of fear extinction

    Institute of Scientific and Technical Information of China (English)

    Lingzhi Kong; Xihong Wu; Liang Li

    2008-01-01

    Fear extinction is an important form of emotional learning, and affects neural plasticity. Cue fear extinction is a classical form of inhibitory learning that can be used as an exposure-based treatment for phobia, because the long-term extinction memory produced during cue fear extinction can limit the over-expression of fear. The expression of this inhibitory memory partly depends on the context in which the extinction learning occurs. Studies such as transient inhibition, electrophysiology and brain imaging have proved that the hippocampus - an important structure in the limbic system - facilitates memory retrieval by contextual cues.Mediation of the hippocampus-medial prefrontal lobe circuit may be the neurobiological basis of this process.This article has reviewed the role of the hippocampus in the learning and retrieval of fear extinction.Contextual modulation of fear extinction may rely on a neural network consisting of the hippocampus, the medial prefrontal cortex and the amygdala.

  15. Cannabinoid facilitation of fear extinction memory recall in humans

    Science.gov (United States)

    Rabinak, Christine A.; Angstadt, Mike; Sripada, Chandra S.; Abelson, James L.; Liberzon, Israel; Milad, Mohammed R.; Phan, K. Luan

    2012-01-01

    A first-line approach to treat anxiety disorders is exposure-based therapy, which relies on extinction processes such as repeatedly exposing the patient to stimuli (conditioned stimuli; CS) associated with the traumatic, fear-related memory. However, a significant number of patients fail to maintain their gains, partly attributed to the fact that this inhibitory learning and its maintenance is temporary and conditioned fear responses can return. Animal studies have shown that activation of the cannabinoid system during extinction learning enhances fear extinction and its retention. Specifically, CB1 receptor agonists, such as Δ9-tetrahydrocannibinol (THC), can facilitate extinction recall by preventing recovery of extinguished fear in rats. However, this phenomenon has not been investigated in humans. We conducted a study using a randomized, double-blind, placebo-controlled, between-subjects design, coupling a standard Pavlovian fear extinction paradigm and simultaneous skin conductance response (SCR) recording with an acute pharmacological challenge with oral dronabinol (synthetic THC) or placebo (PBO) 2 hours prior to extinction learning in 29 healthy adult volunteers (THC = 14; PBO = 15) and tested extinction retention 24 hours after extinction learning. Compared to subjects that received PBO, subjects that received THC showed low SCR to a previously extinguished CS when extinction memory recall was tested 24 hours after extinction learning, suggesting that THC prevented the recovery of fear. These results provide the first evidence that pharmacological enhancement of extinction learning is feasible in humans using cannabinoid system modulators, which may thus warrant further development and clinical testing. PMID:22796109

  16. Altered activation of the antagonist muscle during practice compromises motor learning in older adults

    OpenAIRE

    Chen, Yen-Ting; Kwon, MinHyuk; Fox, Emily J.; Christou, Evangelos A.

    2014-01-01

    Aging impairs the activation of muscle; however, it remains unclear whether it contributes to deficits in motor learning in older adults. The purpose of this study was to determine whether altered activation of antagonistic muscles in older adults during practice inhibits their ability to transfer a motor task ipsilaterally. Twenty young (25.1 ± 3.9 yr; 10 men, 10 women) and twenty older adults (71.5 ± 4.8 yr; 10 men, 10 women) participated. Half of the subjects practiced 100 trials of a rapi...

  17. Altered risk-based decision making following adolescent alcohol use results from an imbalance in reinforcement learning in rats.

    Directory of Open Access Journals (Sweden)

    Jeremy J Clark

    Full Text Available Alcohol use during adolescence has profound and enduring consequences on decision-making under risk. However, the fundamental psychological processes underlying these changes are unknown. Here, we show that alcohol use produces over-fast learning for better-than-expected, but not worse-than-expected, outcomes without altering subjective reward valuation. We constructed a simple reinforcement learning model to simulate altered decision making using behavioral parameters extracted from rats with a history of adolescent alcohol use. Remarkably, the learning imbalance alone was sufficient to simulate the divergence in choice behavior observed between these groups of animals. These findings identify a selective alteration in reinforcement learning following adolescent alcohol use that can account for a robust change in risk-based decision making persisting into later life.

  18. Prenatal exposure to gamma/neutron irradiation: Sensorimotor alterations and paradoxical effects on learning

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    Di Cicco, D.; Antal, S.; Ammassari-Teule, M. (Istituto di Psicobiologia e Psicofarmacologia del CNR, Rome (Italy))

    1991-01-01

    The effects of prenatal exposure on gamma/neutron radiations (0.5 Gy at about the 18th day of fetal life) were studied in a hybrid strain of mice (DBA/Cne males x C57BL/Cne females). During ontogeny, measurements of sensorimotor reflexes revealed in prenatally irradiated mice (1) a delay in sensorial development, (2) deficits in tests involving body motor control, and (3) a reduction of both motility and locomotor activity scores. In adulthood, the behaviour of prenatally irradiated and control mice was examined in the open field test and in reactivity to novelty. Moreover, their learning performance was compared in several situations. The results show that, in the open field test, only rearings were more frequent in irradiated mice. In the presence of a novel object, significant sex x treatment interactions were observed since ambulation and leaning against the novel object increased in irradiated females but decreased in irradiated males. Finally, when submitted to different learning tasks, irradiated mice were impaired in the radial maze, but paradoxically exhibited higher avoidance scores than control mice, possibly because of their low pain thresholds. Taken together, these observations indicate that late prenatal gamma/neutron irradiation induces long lasting alterations at the sensorimotor level which, in turn, can influence learning abilities of adult mice.

  19. The use of cognitive enhancers in animal models of fear extinction.

    Science.gov (United States)

    Kaplan, Gary B; Moore, Katherine A

    2011-08-01

    In anxiety disorders, such as posttraumatic stress disorders and phobias, classical conditioning pairs natural (unconditioned) fear-eliciting stimuli with contextual or discrete cues resulting in enduring fear responses to multiple stimuli. Extinction is an active learning process that results in a reduction of conditioned fear responses after conditioned stimuli are no longer paired with unconditioned stimuli. Fear extinction often produces incomplete effects and this highlights the relative permanence of bonds between conditioned stimuli and conditioned fear responses. The animal research literature is rich in its demonstration of cognitive enhancing agents that alter fear extinction. This review specifically examines the fear extinguishing effects of cognitive enhancers that act on gamma-aminobutyric acid (GABA), glutamatergic, cholinergic, adrenergic, dopaminergic, and cannabinoid signaling pathways. It also examines the effects of compounds that alter epigenetic and neurotrophic mechanisms in fear extinction. Of these cognitive enhancers, glutamatergic N-methyl d-aspartate (NMDA) receptor agonists, such as D-cycloserine, have enhanced fear extinction in a context-, dose- and time-dependent manner. Agents that function as glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor agonists, alpha2-adrenergic receptor antagonists (such as yohimbine), neurotrophic factors (brain derived neurotrophic factor or BDNF) and histone deacetylase inhibitors (valproate and sodium butyrate) also improve fear extinction in animals. However, some have anxiogenic effects and their contextual and temporal effects need to be more reliably demonstrated. Various cognitive enhancers produce changes in cortico-amygdala synaptic plasticity through multiple mechanisms and these neural changes enhance fear extinction. We need to better define the changes in neural plasticity produced by these agents in order to develop more effective compounds. In the clinical

  20. Fear extinction and BDNF: translating animal models of PTSD to the clinic.

    Science.gov (United States)

    Andero, R; Ressler, K J

    2012-07-01

    Brain-derived neurotrophic factor (BDNF) is the most studied neurotrophin involved in synaptic plasticity processes that are required for long-term learning and memory. Specifically, BDNF gene expression and activation of its high-affinity tropomyosin-related kinase B (TrkB) receptor are necessary in the amygdala, hippocampus and prefrontal cortex for the formation of emotional memories, including fear memories. Among the psychiatric disorders with altered fear processing, there is post-traumatic stress disorder (PTSD) which is characterized by an inability to extinguish fear memories. Since BDNF appears to enhance extinction of fear, targeting impaired extinction in anxiety disorders such as PTSD via BDNF signalling may be an important and novel way to enhance treatment efficacy. The aim of this review is to provide a translational point of view that stems from findings in the BDNF regulation of synaptic plasticity and fear extinction. In addition, there are different systems that seem to alter fear extinction through BDNF modulation like the endocannabinoid system and the hypothalamic-pituitary adrenal axis. Recent work also finds that the pituitary adenylate cyclase-activating polypeptide and PAC1 receptor, which are upstream of BDNF activation, may be implicated in PTSD. Especially interesting are data that exogenous fear extinction enhancers such as antidepressants, histone deacetylases inhibitors and D-cycloserine, a partial N-methyl d-aspartate agonist, may act through or in concert with the BDNF-TrkB system. Finally, we review studies where recombinant BDNF and a putative TrkB agonist, 7,8-dihydroxyflavone, may enhance extinction of fear. These approaches may lead to novel agents that improve extinction in animal models and eventually humans.

  1. Altered synaptic plasticity in Tourette's syndrome and its relationship to motor skill learning.

    Directory of Open Access Journals (Sweden)

    Valerie Cathérine Brandt

    Full Text Available Gilles de la Tourette syndrome is a neuropsychiatric disorder characterized by motor and phonic tics that can be considered motor responses to preceding inner urges. It has been shown that Tourette patients have inferior performance in some motor learning tasks and reduced synaptic plasticity induced by transcranial magnetic stimulation. However, it has not been investigated whether altered synaptic plasticity is directly linked to impaired motor skill acquisition in Tourette patients. In this study, cortical plasticity was assessed by measuring motor-evoked potentials before and after paired associative stimulation in 14 Tourette patients (13 male; age 18-39 and 15 healthy controls (12 male; age 18-33. Tic and urge severity were assessed using the Yale Global Tic Severity Scale and the Premonitory Urges for Tics Scale. Motor learning was assessed 45 minutes after inducing synaptic plasticity and 9 months later, using the rotary pursuit task. On average, long-term potentiation-like effects in response to the paired associative stimulation were present in healthy controls but not in patients. In Tourette patients, long-term potentiation-like effects were associated with more and long-term depression-like effects with less severe urges and tics. While motor learning did not differ between patients and healthy controls 45 minutes after inducing synaptic plasticity, the learning curve of the healthy controls started at a significantly higher level than the Tourette patients' 9 months later. Induced synaptic plasticity correlated positively with motor skills in healthy controls 9 months later. The present study confirms previously found long-term improvement in motor performance after paired associative stimulation in healthy controls but not in Tourette patients. Tourette patients did not show long-term potentiation in response to PAS and also showed reduced levels of motor skill consolidation after 9 months compared to healthy controls. Moreover

  2. A new stress model, a scream sound, alters learning and monoamine levels in rat brain.

    Science.gov (United States)

    Hu, Lili; Yang, Juan; Song, Tusheng; Hou, Ni; Liu, Yong; Zhao, Xiaoge; Zhang, Dianzeng; Wang, Lumin; Wang, Tao; Huang, Chen

    2014-01-17

    Most existing animal models for stress involve the simultaneous application of physical and psychological stress factors. In the current study, we described and used a novel psychological stress model (scream sound stress). To study the validity of it, we carried out acute and chronic scream sound stress. First, adult Sprague-Dawley (SD) rats were randomly divided into white noise, stress and background groups. The white noise group and stress group were treated with white noise and scream sound for 4h in the morning respectively. Compared with white noise and background groups, exposure to acute scream sound increased corticosterone (CORT) level and decreased latency in Morris water maze (MWM) test. The levels of noradrenaline (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were altered in the striatum, hypothalamus and hippocampus of stress rats. Second, adult SD rats were randomly divided into background and stress groups, which were treated with scream sound for three weeks. Exposure to chronic scream sound suppressed body weight gain, increased corticosterone (CORT) level, influenced the morphology of adrenal gland, improved spleen and thymus indices, and decreased latency in MWM test. NE, DA, DOPAC, HVA and 5-HIAA levels were also altered in the brain of stress rats. Our results suggested that scream sound, as a novel stressor, facilitated learning ability, as well as altered monoamine levels in the rat brain. Moreover, scream sound is easy to apply and can be applied in more animals at the same time.

  3. Altered activation of the antagonist muscle during practice compromises motor learning in older adults.

    Science.gov (United States)

    Chen, Yen-Ting; Kwon, MinHyuk; Fox, Emily J; Christou, Evangelos A

    2014-08-15

    Aging impairs the activation of muscle; however, it remains unclear whether it contributes to deficits in motor learning in older adults. The purpose of this study was to determine whether altered activation of antagonistic muscles in older adults during practice inhibits their ability to transfer a motor task ipsilaterally. Twenty young (25.1 ± 3.9 yr; 10 men, 10 women) and twenty older adults (71.5 ± 4.8 yr; 10 men, 10 women) participated. Half of the subjects practiced 100 trials of a rapid goal-directed task with ankle dorsiflexion and were tested 1 day later with elbow flexion (transfer). The rest did not perform any ankle practice and only performed the task with elbow flexion. The goal-directed task consisted of rapid movement (180 ms) to match a spatiotemporal target. For each limb, we recorded the EMG burst activity of the primary agonist and antagonist muscles. The rate of improvement during task acquisition (practice) was similar for young and older adults (P > 0.3). In contrast, only young adults were able to transfer the task to the upper limb. Specifically, young adults who practiced ankle dorsiflexion exhibited ∼30% (P movement error and ∼60% (P adults who received equal practice and young adults who did not receive any ankle dorsiflexion practice. These results provide novel evidence that the deficient motor learning in older adults may be related to a differential activation of the antagonist muscle, which compromises their ability to acquire the task during practice.

  4. Deepened Extinction following Compound Stimulus Presentation: Noradrenergic Modulation

    Science.gov (United States)

    Janak, Patricia H.; Corbit, Laura H.

    2011-01-01

    Behavioral extinction is an active form of new learning involving the prediction of nonreward where reward has previously been present. The expression of extinction learning can be disrupted by the presentation of reward itself or reward-predictive stimuli (reinstatement) as well as the passage of time (spontaneous recovery) or contextual changes…

  5. Gradual extinction reduces Reinstatement

    Directory of Open Access Journals (Sweden)

    Youssef eShiban

    2015-09-01

    Full Text Available The current study investigated whether gradually reducing the frequency of aversive stimuli during extinction can prevent the return of fear. Thirty-one participants of a three-stage procedure (acquisition, extinction and a reinstatement test on day two were randomly assigned to a standard extinction (SE and gradual extinction (GE procedure. The two groups differed only in the extinction procedure. While the SE group ran through a regular extinction process without any negative events, the frequency of the aversive stimuli during the extinction phase was gradually reduced for the GE group. The unconditioned stimulus was an air blast (5 bar, 10 ms. A spider and a scorpion were used as conditioned stimuli. The outcome variables were contingency ratings and physiological measures (skin conductance response and startle response. There were no differences found between the two groups for the acquisition and extinction phases concerning contingency ratings, SCR, or startle response. Gradual extinction compared to standard extinction significantly reduced the return of fear in the reinstatement test for the startle response but not for skin conductance response or contingency ratings. This study was successful in translating the findings in rodent to humans. The results suggest that the gradual extinction process is suitable for increasing the efficacy of fear extinction.

  6. Can fear extinction be enhanced? A review of pharmacological and behavioral findings.

    Science.gov (United States)

    Fitzgerald, Paul J; Seemann, Jocelyn R; Maren, Stephen

    2014-06-01

    There is considerable interest, from both a basic and clinical standpoint, in gaining a greater understanding of how pharmaceutical or behavioral manipulations alter fear extinction in animals. Not only does fear extinction in rodents model exposure therapy in humans, where the latter is a cornerstone of behavioral intervention for anxiety disorders such as post-traumatic stress disorder and specific phobias, but also understanding more about extinction provides basic information into learning and memory processes and their underlying circuitry. In this paper, we briefly review three principal approaches that have been used to modulate extinction processes in animals and humans: a purely pharmacological approach, the more widespread approach of combining pharmacology with behavior, and a purely behavioral approach. The pharmacological studies comprise modulation by: brain derived neurotrophic factor (BDNF), d-cycloserine, serotonergic and noradrenergic drugs, neuropeptides, endocannabinoids, glucocorticoids, histone deacetylase (HDAC) inhibitors, and others. These studies strongly suggest that extinction can be modulated by drugs, behavioral interventions, or their combination, although not always in a lasting manner. We suggest that pharmacotherapeutic manipulations provide considerable promise for promoting effective and lasting fear reduction in individuals with anxiety disorders. This article is part of a Special Issue entitled 'Memory enhancement'.

  7. Social defeat: impact on fear extinction and amygdala-prefrontal cortical theta synchrony in 5-HTT deficient mice.

    Science.gov (United States)

    Narayanan, Venu; Heiming, Rebecca S; Jansen, Friederike; Lesting, Jörg; Sachser, Norbert; Pape, Hans-Christian; Seidenbecher, Thomas

    2011-01-01

    Emotions, such as fear and anxiety, can be modulated by both environmental and genetic factors. One genetic factor is for example the genetically encoded variation of the serotonin transporter (5-HTT) expression. In this context, the 5-HTT plays a key role in the regulation of central 5-HT neurotransmission, which is critically involved in the physiological regulation of emotions including fear and anxiety. However, a systematic study which examines the combined influence of environmental and genetic factors on fear-related behavior and the underlying neurophysiological basis is missing. Therefore, in this study we used the 5-HTT-deficient mouse model for studying emotional dysregulation to evaluate consequences of genotype specific disruption of 5-HTT function and repeated social defeat for fear-related behaviors and corresponding neurophysiological activities in the lateral amygdala (LA) and infralimbic region of the medial prefrontal cortex (mPFC) in male 5-HTT wild-type (+/+), homo- (-/-) and heterozygous (+/-) mice. Naive males and experienced losers (generated in a resident-intruder paradigm) of all three genotypes, unilaterally equipped with recording electrodes in LA and mPFC, underwent a Pavlovian fear conditioning. Fear memory and extinction of conditioned fear was examined while recording neuronal activity simultaneously with fear-related behavior. Compared to naive 5-HTT+/+ and +/- mice, 5-HTT-/- mice showed impaired recall of extinction. In addition, 5-HTT-/- and +/- experienced losers showed delayed extinction learning and impaired recall of extinction. Impaired behavioral responses were accompanied by increased theta synchronization between the LA and mPFC during extinction learning in 5-HTT-/- and +/- losers. Furthermore, impaired extinction recall was accompanied with increased theta synchronization in 5-HTT-/- naive and in 5-HTT-/- and +/- loser mice. In conclusion, extinction learning and memory of conditioned fear can be modulated by both the 5

  8. Social defeat: impact on fear extinction and amygdala-prefrontal cortical theta synchrony in 5-HTT deficient mice.

    Directory of Open Access Journals (Sweden)

    Venu Narayanan

    Full Text Available Emotions, such as fear and anxiety, can be modulated by both environmental and genetic factors. One genetic factor is for example the genetically encoded variation of the serotonin transporter (5-HTT expression. In this context, the 5-HTT plays a key role in the regulation of central 5-HT neurotransmission, which is critically involved in the physiological regulation of emotions including fear and anxiety. However, a systematic study which examines the combined influence of environmental and genetic factors on fear-related behavior and the underlying neurophysiological basis is missing. Therefore, in this study we used the 5-HTT-deficient mouse model for studying emotional dysregulation to evaluate consequences of genotype specific disruption of 5-HTT function and repeated social defeat for fear-related behaviors and corresponding neurophysiological activities in the lateral amygdala (LA and infralimbic region of the medial prefrontal cortex (mPFC in male 5-HTT wild-type (+/+, homo- (-/- and heterozygous (+/- mice. Naive males and experienced losers (generated in a resident-intruder paradigm of all three genotypes, unilaterally equipped with recording electrodes in LA and mPFC, underwent a Pavlovian fear conditioning. Fear memory and extinction of conditioned fear was examined while recording neuronal activity simultaneously with fear-related behavior. Compared to naive 5-HTT+/+ and +/- mice, 5-HTT-/- mice showed impaired recall of extinction. In addition, 5-HTT-/- and +/- experienced losers showed delayed extinction learning and impaired recall of extinction. Impaired behavioral responses were accompanied by increased theta synchronization between the LA and mPFC during extinction learning in 5-HTT-/- and +/- losers. Furthermore, impaired extinction recall was accompanied with increased theta synchronization in 5-HTT-/- naive and in 5-HTT-/- and +/- loser mice. In conclusion, extinction learning and memory of conditioned fear can be modulated

  9. Is extinction forever?

    Science.gov (United States)

    Smith-Patten, Brenda D; Bridge, Eli S; Crawford, Priscilla H C; Hough, Daniel J; Kelly, Jeffrey F; Patten, Michael A

    2015-05-01

    Mistrust of science has seeped into public perception of the most fundamental aspect of conservation-extinction. The term ought to be straightforward, and yet, there is a disconnect between scientific discussion and public views. This is not a mere semantic issue, rather one of communication. Within a population dynamics context, we say that a species went locally extinct, later to document its return. Conveying our findings matters, for when we use local extinction, an essentially nonsensical phrase, rather than extirpation, which is what is meant, then we contribute to, if not create outright, a problem for public understanding of conservation, particularly as local extinction is often shortened to extinction in media sources. The public that receives the message of our research void of context and modifiers comes away with the idea that extinction is not forever or, worse for conservation as a whole, that an extinction crisis has been invented.

  10. The Infralimbic Cortex Regulates the Consolidation of Extinction after Cocaine Self-Administration

    Science.gov (United States)

    LaLumiere, Ryan T.; Niehoff, Kate E.; Kalivas, Peter W.

    2010-01-01

    The infralimbic cortex (IL) regulates the consolidation of extinction learning for fear conditioning. Whether the IL influences the consolidation of extinction learning for cocaine self-administration is unknown. To address this issue, male Sprague-Dawley rats underwent 2 wk of cocaine self-administration followed by extinction training. On the…

  11. The effects of compound stimulus extinction and inhibition of noradrenaline reuptake on the renewal of alcohol seeking

    OpenAIRE

    Furlong, T M; Pan, M J; Corbit, L H

    2015-01-01

    Alcohol-related stimuli can trigger relapse of alcohol-seeking behaviors even after extended periods of abstinence. Extinction of such stimuli can reduce their impact on relapse; however, the expression of extinction can be disrupted when testing occurs outside the context where extinction learning took place, an effect termed renewal. Behavioral and pharmacological methods have recently been shown to augment extinction learning; yet, it is not known whether the improved expression of extinct...

  12. Effects of sleep on memory for conditioned fear and fear extinction

    OpenAIRE

    Pace-Schott, Edward F.; Germain, Anne; Milad, Mohammed R.

    2015-01-01

    Learning and memory for extinction of conditioned fear is a basic mammalian mechanism for regulating negative emotion. Sleep promotes both the consolidation of memory and the regulation of emotion. Sleep can influence consolidation and modification of memories associated with both fear and its extinction. After brief overviews of the behavior and neural circuitry associated with fear conditioning, extinction learning and extinction memory in the rodent and human, interactions of sleep with th...

  13. Mass extinction: a commentary

    Science.gov (United States)

    Raup, D. M.

    1987-01-01

    Four neocatastrophist claims about mass extinction are currently being debated; they are that: 1, the late Cretaceous mass extinction was caused by large body impact; 2, as many as five other major extinctions were caused by impact; 3, the timing of extinction events since the Permian is uniformly periodic; and 4, the ages of impact craters on Earth are also periodic and in phase with the extinctions. Although strongly interconnected the four claims are independent in the sense that none depends on the others. Evidence for a link between impact and extinction is strong but still needs more confirmation through bed-by-bed and laboratory studies. An important area for future research is the question of whether extinction is a continuous process, with the rate increasing at times of mass extinctions, or whether it is episodic at all scales. If the latter is shown to be generally true, then species are at risk of extinction only rarely during their existence and catastrophism, in the sense of isolated events of extreme stress, is indicated. This is line of reasoning can only be considered an hypothesis for testing. In a larger context, paleontologists may benefit from a research strategy that looks to known Solar System and Galactic phenomena for predictions about environmental effects on earth. The recent success in the recognition of Milankovitch Cycles in the late Pleistocene record is an example of the potential of this research area.

  14. Supramammillary serotonin reduction alters place learning and concomitant hippocampal, septal, and supramammillar theta activity in a Morris water maze

    Science.gov (United States)

    Hernández-Pérez, J. Jesús; Gutiérrez-Guzmán, Blanca E.; López-Vázquez, Miguel Á.; Olvera-Cortés, María E.

    2015-01-01

    Hippocampal theta activity is related to spatial information processing, and high-frequency theta activity, in particular, has been linked to efficient spatial memory performance. Theta activity is regulated by the synchronizing ascending system (SAS), which includes mesencephalic and diencephalic relays. The supramamillary nucleus (SUMn) is located between the reticularis pontis oralis and the medial septum (MS), in close relation with the posterior hypothalamic nucleus (PHn), all of which are part of this ascending system. It has been proposed that the SUMn plays a role in the modulation of hippocampal theta-frequency; this could occur through direct connections between the SUMn and the hippocampus or through the influence of the SUMn on the MS. Serotonergic raphe neurons prominently innervate the hippocampus and several components of the SAS, including the SUMn. Serotonin desynchronizes hippocampal theta activity, and it has been proposed that serotonin may regulate learning through the modulation of hippocampal synchrony. In agreement with this hypothesis, serotonin depletion in the SUMn/PHn results in deficient spatial learning and alterations in CA1 theta activity-related learning in a Morris water maze. Because it has been reported that SUMn inactivation with lidocaine impairs the consolidation of reference memory, we asked whether changes in hippocampal theta activity related to learning would occur through serotonin depletion in the SUMn, together with deficiencies in memory. We infused 5,7-DHT bilaterally into the SUMn in rats and evaluated place learning in the standard Morris water maze task. Hippocampal (CA1 and dentate gyrus), septal and SUMn EEG were recorded during training of the test. The EEG power in each region and the coherence between the different regions were evaluated. Serotonin depletion in the SUMn induced deficient spatial learning and altered the expression of hippocampal high-frequency theta activity. These results provide evidence in

  15. A window of vulnerability: impaired fear extinction in adolescence.

    Science.gov (United States)

    Baker, Kathryn D; Den, Miriam L; Graham, Bronwyn M; Richardson, Rick

    2014-09-01

    There have been significant advances made towards understanding the processes mediating extinction of learned fear. However, despite being of clear theoretical and clinical significance, very few studies have examined fear extinction in adolescence, which is often described as a developmental window of vulnerability to psychological disorders. This paper reviews the relatively small body of research examining fear extinction in adolescence. A prominent finding of this work is that adolescents, both humans and rodents, exhibit a marked impairment in extinction relative to both younger (e.g., juvenile) and older (e.g., adult) groups. We then review some potential mechanisms that could produce the striking extinction deficit observed in adolescence. For example, one neurobiological candidate mechanism for impaired extinction in adolescence involves changes in the functional connectivity within the fear extinction circuit, particularly between prefrontal cortical regions and the amygdala. In addition, we review research on emotion regulation and attention processes that suggests that developmental changes in attention bias to threatening cues may be a cognitive mechanism that mediates age-related differences in extinction learning. We also examine how a differential reaction to chronic stress in adolescence impacts upon extinction retention during adolescence as well as in later life. Finally, we consider the findings of several studies illustrating promising approaches that overcome the typically-observed extinction impairments in adolescent rodents and that could be translated to human adolescents.

  16. Extinction of chained instrumental behaviors: Effects of consumption extinction on procurement responding.

    Science.gov (United States)

    Thrailkill, Eric A; Bouton, Mark E

    2016-03-01

    Operant behavior is typically organized into sequences of responses that eventually lead to a reinforcer. Response elements can be categorized as those that directly lead to reward consumption (i.e., a consumption response) and those that lead to the opportunity to make the consumption response (i.e., a procurement response). These responses often differ topographically and in terms of the discriminative stimuli that set the occasion for them. We have recently shown that extinction of the procurement response acts to weaken the specific associated consumption response, and that active inhibition of the procurement response is required for this effect. To expand the analysis of the associative structure of chains, in the present experiments we asked the reverse question: whether extinction of consumption behavior results in a decrease in the associated procurement response in a discriminated heterogeneous chain. In Experiment 1, extinction of consumption alone led to an attenuation of the associated procurement response only when rats were allowed to make the consumption response in extinction. Exposure to the consumption stimulus alone was not sufficient to produce weakened procurement responding. In Experiment 2, rats learned two distinct heterogeneous chains, and extinction of one consumption response specifically weakened the procurement response associated with it. The results add to the evidence suggesting that rats learn a highly specific associative structure in behavior chains, emphasizing the role of learning response inhibition in extinction.

  17. Timing, tempo and paleoenvironmental implications of Deccan volcanism relative to the KTB extinction, what we can learn from the red bole record?

    Science.gov (United States)

    Adatte, Thierry; Sordet, Valentin; Keller, Gerta; Schoene, Blair; Samperton, Kyle; Khadri, Syed

    2016-04-01

    Deccan Traps erupted in three main phases with 6% total Deccan volume in phase-1 (C30n), 80% in phase-2 (C29r) and 14% in phase-3 (C29n). Recent studies indicate that the bulk (80%) of Deccan trap eruptions (phase-2) occurred over a relatively short time interval in magnetic polarity C29r. U-Pb zircon geochronology shows that the main phase-2 began 250 ky before the Cretaceous-Tertiary (KT) mass extinction and continued into the early Danian suggesting a cause-and-effect relationship. In India a strong floral response is observed as a direct consequence of volcanic phase-2. Shortly after the onset of Deccan phase-2, the floral association dominated by gymnosperms and angiosperms was decimated as indicated by a sharp decrease in pollen and spores coupled with the appearance of fungi, which mark increasing stress conditions as a direct result of volcanic activity. The inter-trappean sediments deposited in phase-2 are characterized by the highest alteration CIA index values suggesting increased acid rains due to SO2 emissions. In addition, a sharp decrease in pollen and spores coupled with the appearance of fungi mark increasing stress conditions, which are likely a direct result of volcanic activity. Bulk organic geochemistry points to a strong degradation of the indigenous organic matter, suggesting that the biomass was oxidized in acidic conditions triggered by intense volcanic activity. Closer to the eruption center, the lava flows are generally separated by red weathered horizons known as red boles that mark quiescent periods between basalt flows. Red boles have increasingly attracted the attention of researchers to understand the climatic and paleoenvironmental impact of Continental Flood Basalts (CFB). Recent advances in U-Pb dating of Deccan lava flows, studies of weathering patterns and paleoclimatic information gained from multiproxy analyses of red bole beds (e.g., lithology, mineralogy, geochemistry) yield crucial evidence of environmental changes

  18. Extinction and renewal of conditioned sexual responses

    NARCIS (Netherlands)

    Brom, M.; Laan, E.; Everaerd, W.; Spinhoven, P.; Both, S.

    2014-01-01

    INTRODUCTION: Extinction involves an inhibitory form of new learning that is highly dependent on the context for expression. This is supported by phenomena such as renewal and spontaneous recovery, which may help explain the persistence of appetitive behavior, and related problems such as addictions

  19. Extinction debt in source-sink metacommunities.

    Directory of Open Access Journals (Sweden)

    Nicolas Mouquet

    Full Text Available In an increasingly modified world, understanding and predicting the consequences of landscape alteration on biodiversity is a challenge for ecologists. To this end, metacommunity theory has developed to better understand the complexity of local and regional interactions that occur across larger landscapes. While metacommunity ecology has now provided several alternative models of species coexistence at different spatial scales, predictions regarding the consequences of landscape alteration have been done exclusively for the competition-colonization trade off model (CC. In this paper we investigate the effects of landscape perturbation on source-sink metacommunities. We show that habitat destruction perturbs the equilibria among species competitive effects within the metacommunity, driving both direct extinctions and an indirect extinction debt. As in CC models, we found a time lag for extinction following habitat destruction that varied in length depending upon the relative importance of direct and indirect effects. However, in contrast to CC models, we found that the less competitive species are more affected by habitat destruction. The best competitors can sometimes even be positively affected by habitat destruction, which corresponds well with the results of field studies. Our results are complementary to those results found in CC models of metacommunity dynamics. From a conservation perspective, our results illustrate that landscape alteration jeopardizes species coexistence in patchy landscapes through complex indirect effects and delayed extinctions patterns.

  20. [GABA-Receptors in Modulation of Fear Memory Extinction].

    Science.gov (United States)

    Dubrovina, N I

    2016-01-01

    GABA is the major inhibitory neurotransmitter in the central nervous system determining the efficacy of neuronal interaction. GABA-receptors play a key role in different aspects of fear memory--acquisition and consolidation, retention, reconsolidation and extinction. Extinction is an important behavioural phenomenon which allows organism to adapt its behavior to a changing environment. Extinction of fear memory is a form of new inhibitory learning which interferes with expression of the initial acquired fear conditioning. Resistance to extinction is symptom of depression and posttraumatic stress disorder. The aim of the present review was to summarize own and literary data about GABAergic modulation of fear extinction and pharmacological correction of extinction impairment at influences on GABA(A)- and GABA(B)- receptors.

  1. Role of Medial Prefrontal Cortex Narp in the Extinction of Morphine Conditioned Place Preference

    Science.gov (United States)

    Blouin, Ashley M.; Han, Sungho; Pearce, Anne M.; Cheng, KaiLun; Lee, JongAh J.; Johnson, Alexander W.; Wang, Chuansong; During, Matthew J.; Holland, Peter C.; Shaham, Yavin; Baraban, Jay M.; Reti, Irving M.

    2013-01-01

    Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus…

  2. LDA merging and splitting with applications to multiagent cooperative learning and system alteration.

    Science.gov (United States)

    Pang, Shaoning; Ban, Tao; Kadobayashi, Youki; Kasabov, Nikola K

    2012-04-01

    To adapt linear discriminant analysis (LDA) to real-world applications, there is a pressing need to equip it with an incremental learning ability to integrate knowledge presented by one-pass data streams, a functionality to join multiple LDA models to make the knowledge sharing between independent learning agents more efficient, and a forgetting functionality to avoid reconstruction of the overall discriminant eigenspace caused by some irregular changes. To this end, we introduce two adaptive LDA learning methods: LDA merging and LDA splitting. These provide the benefits of ability of online learning with one-pass data streams, retained class separability identical to the batch learning method, high efficiency for knowledge sharing due to condensed knowledge representation by the eigenspace model, and more preferable time and storage costs than traditional approaches under common application conditions. These properties are validated by experiments on a benchmark face image data set. By a case study on the application of the proposed method to multiagent cooperative learning and system alternation of a face recognition system, we further clarified the adaptability of the proposed methods to complex dynamic learning tasks.

  3. Acute stress impairs the retrieval of extinction memory in humans.

    Science.gov (United States)

    Raio, Candace M; Brignoni-Perez, Edith; Goldman, Rachel; Phelps, Elizabeth A

    2014-07-01

    Extinction training is a form of inhibitory learning that allows an organism to associate a previously aversive cue with a new, safe outcome. Extinction does not erase a fear association, but instead creates a competing association that may or may not be retrieved when a cue is subsequently encountered. Characterizing the conditions under which extinction learning is expressed is important to enhancing the treatment of anxiety disorders that rely on extinction-based exposure therapy as a primary treatment technique. The ventromedial prefrontal cortex, which plays a critical role in the expression of extinction memory, has been shown to be functionally impaired after stress exposure. Further, recent work in rodents has demonstrated that exposure to stress leads to deficits in extinction retrieval, although this has yet to be tested in humans. To explore how stress might influence extinction retrieval in humans, participants underwent a differential aversive learning paradigm, in which one image was probabilistically paired with an aversive shock while the other image denoted safety. Extinction training directly followed, at which point reinforcement was omitted. A day later, participants returned to the lab and either completed an acute stress manipulation (i.e., cold pressor), or a control task, before undergoing an extinction retrieval test. Skin conductance responses and salivary cortisol concentrations were measured throughout each session as indices of fear arousal and neuroendocrine stress response, respectively. The efficacy of our stress induction was established by observing significant increases in cortisol for the stress condition only. We examined extinction retrieval by comparing conditioned responses during the last trial of extinction (day 1) with that of the first trial of re-extinction (day 2). Groups did not differ on initial fear acquisition or extinction, however, a day later participants in the stress group (n=27) demonstrated significantly

  4. Differential Regulation of Glutamic Acid Decarboxylase Gene Expression after Extinction of a Recent Memory vs. Intermediate Memory

    Science.gov (United States)

    Sangha, Susan; Ilenseer, Jasmin; Sosulina, Ludmila; Lesting, Jorg; Pape, Hans-Christian

    2012-01-01

    Extinction reduces fear to stimuli that were once associated with an aversive event by no longer coupling the stimulus with the aversive event. Extinction learning is supported by a network comprising the amygdala, hippocampus, and prefrontal cortex. Previous studies implicate a critical role of GABA in extinction learning, specifically the GAD65…

  5. The expression of c-Fos and colocalisation of c-Fos and glucocorticoid receptors in brain structures of low and high anxiety rats subjected to extinction trials and re-learning of a conditioned fear response.

    Science.gov (United States)

    Lehner, Małgorzata; Wisłowska-Stanek, Aleksandra; Taracha, Ewa; Maciejak, Piotr; Szyndler, Janusz; Skórzewska, Anna; Turzyńska, Danuta; Sobolewska, Alicja; Hamed, Adam; Bidziński, Andrzej; Płaźnik, Adam

    2009-11-01

    We designed an animal model to examine the mechanisms of differences in individual responses to aversive stimuli. We used the rat freezing response in the context fear test as a discriminating variable: low responders (LR) were defined as rats with a duration of freezing response one standard error or more below the mean value, and high responders (HR) were defined as rats with a duration of freezing response one standard error or more above the mean value. We sought to determine the colocalisation of c-Fos and glucocorticoid receptors-immunoreactivity (GR-ir) in HR and LR rats subjected to conditioned fear training, two extinction sessions and re-learning of a conditioned fear. We found that HR animals showed a marked decrease in conditioned fear in the course of two extinction sessions (16 days) in comparison with the control and LR groups. The LR group exhibited higher activity in the cortical M2 and prelimbic areas (c-Fos) and had an increased number of cells co-expressing c-Fos and GR-ir in the M2 and medial orbital cortex after re-learning a contextual fear. HR rats showed increased expression of c-Fos, GR-ir and c-Fos/GR-ir colocalised neurons in the basolateral amygdala and enhanced c-Fos and GR-ir in the dentate gyrus (DG) in comparison with LR animals. Our data indicate that recovery of a context-related behaviour upon re-learning of contextual fear is accompanied in HR animals by a selective increase in c-Fos expression and GRs-ir in the DG area of the hippocampus.

  6. Delayed extinction and stronger drug-primed reinstatement of methamphetamine seeking in rats prenatally exposed to morphine.

    Science.gov (United States)

    Shen, Ying-Ling; Chen, Shao-Tsu; Chan, Tzu-Yi; Hung, Tsai-Wei; Tao, Pao-Luh; Liao, Ruey-Ming; Chan, Ming-Huan; Chen, Hwei-Hsien

    2016-02-01

    Prenatal morphine (PM) affects the development of brain reward system and cognitive function. The present study aimed to determine whether PM exposure increases the vulnerability to MA addiction. Pregnant Sprague-Dawley rats were administered saline or morphine during embryonic days 3-20. The acquisition, extinction and reinstatement of methamphetamine (MA) conditioned place preference (CPP) and intravenous self-administration (SA) paradigms were assessed in the male adult offspring. There was no difference in the acquisition and expression of MA CPP between saline- and PM-exposed rats, whereas PM-exposed rats exhibited slower extinction and greater MA priming-induced reinstatement of drug-seeking behavior than controls. Similarly, MA SA under progressive ratio and fixed ratio schedules was not affected by PM exposure, but PM-exposed rats required more extinction sessions to reach the extinction criteria and displayed more severe MA priming-, but not cue-induced, reinstatement. Such alterations in extinction and reinstatement were not present when PM-exposed rats were tested in an equivalent paradigm assessing operant responding for food pellets. Our results demonstrate that PM exposure did not affect the association memory formation during acquisition of MA CPP or SA, but impaired extinction learning and increased MA-primed reinstatement in both tasks. These findings suggest that the offspring of women using morphine or heroin during pregnancy might predict persistent MA seeking during extinction and enhanced propensity to MA relapse although they might not be more susceptible to the reinforcing effect of MA during initiation of drug use.

  7. Stimulation of the human motor cortex alters generalization patterns of motor learning

    OpenAIRE

    Orban de Xivry, Jean-Jacques; Marko, Mollie K; Pekny, Sarah E.; Pastor, Damien; Izawa, Jun; Celnik, Pablo; Shadmehr, Reza

    2011-01-01

    It has been hypothesized that the generalization patterns that accompany learning carry the signatures of the neural systems that are engaged in that learning. Reach adaptation in force fields has generalization patterns that suggest primary engagement of a neural system that encodes movements in the intrinsic coordinates of joints and muscles, and lesser engagement of a neural system that encodes movements in the extrinsic coordinates of the task. Among the cortical motor areas, the intrinsi...

  8. Insecticide imidacloprid influences cognitive functions and alters learning performance and related gene expression in a rat model.

    Science.gov (United States)

    Kara, Murat; Yumrutas, Onder; Demir, Caner F; Ozdemir, Hasan Huseyin; Bozgeyik, Ibrahim; Coskun, Salih; Eraslan, Ersen; Bal, Ramazan

    2015-10-01

    The potential toxic effects of several pesticides, including imidacloprid on non-target organisms have not been clearly established. Also, the chronic effects of non-toxic doses on cognitive function in mammals are unknown. In this study, the effects of different doses of imidacloprid on learning and memory of infant and adult rats were evaluated, and the expressions of genes synthesizing proteins known to be associated with learning in brain tissues were also documented. 0.5, 2 and 8 mg/kg doses of imidacloprid were administered to newborn infant and adult Wistar albino rats by gavage. Their learning activities were evaluated, and the expression levels of the inotropic glutamate receptor GRIN1, synoptophysin, growth-associated protein 43 and the muscarinic receptor M1 in hippocampus were determined by real-time PCR method. Learning activities were diminished significantly at 2 and 8 mg/kg doses in the infant model groups and at 8 mg/kg dose in adult rats. Also, expression levels of GRIN1, SYP and GAP-43 were found to be insignificantly altered. Only the expression of M1 were significantly changed in high doses of adult group. Thus imidacloprid in high doses causes deterioration in cognitive functions particularly in infant rats, and this deterioration may be associated with changes in the expressions of related genes.

  9. Contingency awareness shapes acquisition and extinction of emotional responses in a conditioning model of pain-related fear

    Directory of Open Access Journals (Sweden)

    Franziska eLabrenz

    2015-11-01

    CS-. Contingency accuracy predicted variance in the formation of positive responses to safety cues while no predictive value was found for danger cues following acquisition and for neither cue following extinction.Our findings underscore specific roles of learned danger and safety in pain-related acquisition and extinction. Contingency accuracy appears to distinctly impact learned emotional responses to safety and danger cues, supporting aversive learning to occur independently from CS-US awareness. The interplay of cognitive and emotional factors in shaping excitatory and inhibitory pain-related learning may contribute to altered pain processing, underscoring its clinical relevance in chronic pain.

  10. Extinction of chained instrumental behaviors: Effects of procurement extinction on consumption responding.

    Science.gov (United States)

    Thrailkill, Eric A; Bouton, Mark E

    2015-07-01

    Instrumental behavior often consists of sequences or chains of responses that minimally include procurement behaviors that enable subsequent consumption behaviors. In such chains, behavioral units are linked by access to one another and eventually to a primary reinforcer, such as food or a drug. The present experiments examined the effects of extinguishing procurement responding on consumption responding after training of a discriminated heterogeneous instrumental chain. Rats learned to make a procurement response (e.g., pressing a lever) in the presence of a distinctive discriminative stimulus; making that response led to the presentation of a second discriminative stimulus that set the occasion for a consumption response (e.g., pulling a chain), which then produced a food-pellet reinforcer. Experiment 1 showed that extinction of either the full procurement-consumption chain or procurement alone weakened the consumption response tested in isolation. Experiment 2 replicated the procurement extinction effect and further demonstrated that the opportunity to make the procurement response, as opposed to simple exposure to the procurement stimulus alone, was required. In Experiment 3, rats learned 2 distinct discriminated heterogeneous chains; extinction of 1 procurement response specifically weakened the consumption response that had been associated with it. The results suggest that learning to inhibit the procurement response may produce extinction of consumption responding through mediated extinction. The experiments suggest the importance of an associative analysis of instrumental behavior chains. (PsycINFO Database Record

  11. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids.

    Science.gov (United States)

    Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

    2016-05-01

    Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders.

  12. The Memory System Engaged During Acquisition Determines the Effectiveness of Different Extinction Protocols

    OpenAIRE

    Jarid eGoodman; Mark ePackard

    2015-01-01

    Previous research indicates that extinction of rodent maze behavior may occur without explicit performance of the previously required response. In latent extinction, confining an animal to a previously rewarded goal location without reinforcement is typically sufficient to produce extinction of maze learning. However, previous studies have not determined whether latent extinction may be successfully employed to extinguish all types of memory acquired in the maze, or whether only specific typ...

  13. Context-Dependent Human Extinction Memory Is Mediated by a Ventromedial Prefrontal and Hippocampal Network

    OpenAIRE

    Kalisch, R; Korenfeld, E; Stephan, K.E.; Weiskopf, N.; Seymour, B; Dolan, R.J.

    2006-01-01

    In fear extinction, an animal learns that a conditioned stimulus (CS) no longer predicts a noxious stimulus [unconditioned stimulus (UCS)] to which it had previously been associated, leading to inhibition of the conditioned response (CR). Extinction creates a new CS-noUCS memory trace, competing with the initial fear (CS-UCS) memory. Recall of extinction memory and, hence, CR inhibition at later CS encounters is facilitated by contextual stimuli present during extinction training. In line wit...

  14. Evidence that the pattern of visuomotor sequence learning is altered in children with autism.

    Science.gov (United States)

    Gidley Larson, Jennifer C; Mostofsky, Stewart H

    2008-12-01

    Motor deficits are commonly reported in autism, with one of the most consistent findings being impaired execution of skilled movements and gestures. Given the developmental nature of autism, it is possible that deficits in motor/procedural learning contribute to impaired acquisition of motor skills. Thus, careful examination of mechanisms underlying learning and memory may be critical to understanding the neural basis of autism. A previous study reported impaired motor learning in children with high-functioning autism (HFA); however, it is unclear whether the observed deficits in motor learning are due, in part, to impaired motor execution and whether these deficits are specific to autism. In order to examine these questions, 153 children (52 with HFA, 39 with attention-deficit/hyperactivity disorder (ADHD) and 62 typically developing (TD) children) participated in two independent experiments using a Rotary Pursuit task, with change in performance across blocks as a measure of learning. For both tasks, children with HFA demonstrated significantly less change in performance than did TD children, even when differences in motor execution were minimized. Differences in learning were not seen between ADHD and TD groups on either experiment. Analyses of the pattern of findings revealed that compared with both ADHD and TD children, children with HFA showed a similar degree of improvement in performance; however, they showed significantly less decrement in performance when presented with an alternate ("interference") pattern. The findings suggest that mechanisms underlying acquisition of novel movement patterns may differ in children with autism. These findings may help explain impaired skill development in children with autism and help to guide approaches for helping children learn novel motor, social and communicative skills.

  15. Oral contraceptive usage alters the effects of cortisol on implicit fear learning.

    Science.gov (United States)

    Merz, Christian Josef; Tabbert, Katharina; Schweckendiek, Jan; Klucken, Tim; Vaitl, Dieter; Stark, Rudolf; Wolf, Oliver Tobias

    2012-09-01

    An important feature of the human defense system comprises fear learning, which stress hormones can crucially modulate. However, stress hormones might influence men and women differently, in part because of interactions with sex hormones. In women, distinct stages of the menstrual cycle or the intake of oral contraceptives (OC) affect sex hormone levels. In this study, we used a differential fear conditioning paradigm with electrical stimulation as unconditioned stimulus (UCS) following one neutral stimulus (conditioned stimulus, CS+), but not another (CS-).To investigate implicit fear learning, participants were distracted from detecting the contingencies between CS and UCS. To address interaction effects of sex and stress hormones, 32 men, 30 women in the early follicular phase of the menstrual cycle (FO), 30 women in the luteal phase (LU), and 30 OC women received either 30 mg cortisol or a placebo. In the contrast CS+ minus CS-, an interaction between cortisol administration and sex hormone status emerged in the anterior parahippocampal gyrus and the hippocampus. Cortisol reduced fear learning in men, FO, and LU women, but enhanced it in OC women. Additionally, cortisol attenuated differential amygdala activation in the entire group. These results demonstrate that OC usage substantially modifies cortisol effects on emotional learning in women, particularly in memory-related medial temporal lobe regions. Further, a high dose of cortisol reduces amygdala differentiation pointing to a lowered learning ability of the defense system under high cortisol concentrations, irrespective of current sex hormone availability.

  16. The transition from memory retrieval to extinction

    Directory of Open Access Journals (Sweden)

    Cammarota Martín

    2004-01-01

    Full Text Available Memory is measured by measuring retrieval. Retrieval is often triggered by the conditioned stimulus (CS; however, as known since Pavlov, presentation of the CS alone generates extinction. One-trial avoidance (IA is a much used conditioned fear paradigm in which the CS is the safe part of a training apparatus, the unconditioned stimulus (US is a footshock and the conditioned response is to stay in the safe area. In IA, retrieval is measured without the US, as latency to step-down from the safe area (i.e., a platform. Extinction is installed at the moment of the first unreinforced test session, as clearly shown by the fact that many drugs, including PKA, ERK and protein synthesis inhibitors as well as NMDA receptor antagonists, hinder extinction when infused into the hippocampus or the basolateral amygdala at the moment of the first test session but not later. Some, but not all the molecular systems required for extinction are also activated by retrieval, further endorsing the hypothesis that although retrieval is behaviorally and biochemically necessary for the generation of extinction, this last process constitutes a new learning secondary to the unreinforced expression of the original trace.

  17. Requirement for BDNF in the reconsolidation of fear extinction.

    Science.gov (United States)

    Radiske, Andressa; Rossato, Janine I; Köhler, Cristiano A; Gonzalez, Maria Carolina; Medina, Jorge H; Cammarota, Martín

    2015-04-22

    Therapies based on the impairment of reconsolidation or the enhancement of extinction offer the possibility of decreasing the persistent recollection of distressing memories. However, the direct interplay between reconsolidation and extinction has rarely been considered. Previously, we reported that reactivation induces reconsolidation of fear extinction memory. Here, using a step-down inhibitory avoidance learning paradigm in rats, we show that intrahippocampus infusion of function-blocking anti-BDNF antibody immediately or 6 h after extinction memory reactivation impairs the reconsolidation of extinction. Extinction memory reactivation increases proBDNF, BDNF, and tropomyosin receptor kinase B (TrkB) phosphorylation levels in dorsal CA1, while blocking BDNF maturation in the hippocampus with plasminogen activator inhibitor 1 hinders the persistence of extinction and induces the recurrence of fear. Moreover, coinfusion of recombinant BDNF (0.25 μg/side) after extinction memory reactivation impedes the recovery of the avoidance response induced by inhibiting gene expression and protein synthesis in the dorsal hippocampus. Our findings unravel a new role for BDNF, suggesting that this neurotrophin is necessary and sufficient to maintain the reactivated fear extinction engram.

  18. Predation effects on mean time to extinction under demographic stochasticity.

    Science.gov (United States)

    Palamara, Gian Marco; Delius, Gustav W; Smith, Matthew J; Petchey, Owen L

    2013-10-01

    Methods for predicting the probability and timing of a species' extinction are typically based on single species population dynamics. Assessments of extinction risk often lack effects of interspecific interactions. We study a birth and death process in which the death rate includes an effect of predation. Predation is included via a general nonlinear expression for the functional response of predation to prey density. We investigate the effects of the foraging parameters (e.g. attack rate and handling time) on the mean time to extinction. Mean time to extinction varies by orders of magnitude when we alter the foraging parameters, even when we exclude the effects of these parameters on the equilibrium population size. Conclusions are robust to assumptions about initial conditions and variable predator abundance. These findings clearly show that accounting for the nature of interspecific interactions is likely to be critically important when estimating extinction risk.

  19. The role of the amygdala in the extinction of conditioned fear.

    Science.gov (United States)

    Barad, Mark; Gean, Po-Wu; Lutz, Beat

    2006-08-15

    The amygdala has long been known to play a central role in the acquisition and expression of fear. More recently, convergent evidence has implicated the amygdala in the extinction of fear as well. In rodents, some of this evidence comes from the infusion of drugs directly into the amygdala and, in particular, into the basolateral complex of the amygdala, during or after extinction learning. In vivo electrophysiology has identified cellular correlates of extinction learning and memory in the lateral nucleus of that structure. Human imaging experiments also indicate that amygdaloid activity correlates with extinction training. In addition, some studies have directly identified changes in molecular constituents of the basolateral amygdala. Together these experiments strongly indicate that the basolateral amygdala plays a crucial role in extinction learning. Interpreted in the light of these findings, several recent in vitro electrophysiology studies in amygdala-containing brain slices are suggestive of potential synaptic and circuit bases of extinction learning.

  20. Early Developmental Low-Dose Methylmercury Exposure Alters Learning and Memory in Periadolescent but Not Young Adult Rats

    Science.gov (United States)

    Albores-Garcia, Damaris; Hernandez, Alberto J.; Loera, Miriam J.

    2016-01-01

    Few studies have assessed the effects of developmental methylmercury (MeHg) exposure on learning and memory at different ages. The possibility of the amelioration or worsening of the effects has not been sufficiently investigated. This study aimed to assess whether low-dose MeHg exposure in utero and during suckling induces differential disturbances in learning and memory of periadolescent and young adult rats. Four experimental groups of pregnant Sprague-Dawley rats were orally exposed to MeHg or vehicle from gestational day 5 to weaning: (1) control (vehicle), (2) 250 μg/kg/day MeHg, (3) 500 μg/kg/day MeHg, and (4) vehicle, and treated on the test day with MK-801 (0.15 mg/kg i.p.), an antagonist of the N-methyl D-aspartate receptor. The effects were evaluated in male offspring through the open field test, object recognition test, Morris water maze, and conditioned taste aversion. For each test and stage assessed, different groups of animals were used. MeHg exposure, in a dose-dependent manner, disrupted exploratory behaviour, recognition memory, spatial learning, and acquisition of aversive memories in periadolescent rats, but alterations were not observed in littermates tested in young adulthood. These results suggest that developmental low-dose exposure to MeHg induces age-dependent detrimental effects. The relevance of decreasing exposure to MeHg in humans remains to be determined. PMID:26885512

  1. Early Developmental Low-Dose Methylmercury Exposure Alters Learning and Memory in Periadolescent but Not Young Adult Rats

    Directory of Open Access Journals (Sweden)

    Damaris Albores-Garcia

    2016-01-01

    Full Text Available Few studies have assessed the effects of developmental methylmercury (MeHg exposure on learning and memory at different ages. The possibility of the amelioration or worsening of the effects has not been sufficiently investigated. This study aimed to assess whether low-dose MeHg exposure in utero and during suckling induces differential disturbances in learning and memory of periadolescent and young adult rats. Four experimental groups of pregnant Sprague-Dawley rats were orally exposed to MeHg or vehicle from gestational day 5 to weaning: (1 control (vehicle, (2 250 μg/kg/day MeHg, (3 500 μg/kg/day MeHg, and (4 vehicle, and treated on the test day with MK-801 (0.15 mg/kg i.p., an antagonist of the N-methyl D-aspartate receptor. The effects were evaluated in male offspring through the open field test, object recognition test, Morris water maze, and conditioned taste aversion. For each test and stage assessed, different groups of animals were used. MeHg exposure, in a dose-dependent manner, disrupted exploratory behaviour, recognition memory, spatial learning, and acquisition of aversive memories in periadolescent rats, but alterations were not observed in littermates tested in young adulthood. These results suggest that developmental low-dose exposure to MeHg induces age-dependent detrimental effects. The relevance of decreasing exposure to MeHg in humans remains to be determined.

  2. Extinction and renewal of conditioned sexual responses.

    Directory of Open Access Journals (Sweden)

    Mirte Brom

    Full Text Available INTRODUCTION: Extinction involves an inhibitory form of new learning that is highly dependent on the context for expression. This is supported by phenomena such as renewal and spontaneous recovery, which may help explain the persistence of appetitive behavior, and related problems such as addictions. Research on these phenomena in the sexual domain is lacking, where it may help to explain the persistence of learned sexual responses. METHOD: Men (n = 40 and women (n = 62 participated in a differential conditioning paradigm, with genital vibrotactile stimulation as US and neutral pictures as conditional stimuli (CSs. Dependent variables were genital and subjective sexual arousal, affect, US expectancy, and approach and avoid tendencies towards the CSs. Extinction and renewal of conditioned sexual responses were studied by context manipulation (AAA vs. ABA condition. RESULTS: No renewal effect of genital conditioned responding could be detected, but an obvious recovery of US expectancy following a context change after extinction (ABA was demonstrated. Additionally, women demonstrated recovery of subjective affect and subjective sexual arousal. Participants in the ABA demonstrated more approach biases towards stimuli. CONCLUSIONS: The findings support the context dependency of extinction and renewal of conditioned sexual responses in humans. This knowledge may have implications for the treatment of disturbances in sexual appetitive responses such as hypo- and hypersexuality.

  3. Ecological model of extinctions

    CERN Document Server

    Abramson, G

    1997-01-01

    We present numerical results based on a simplified ecological system in evolution, showing features of extinction similar to that claimed for the biosystem on Earth. In the model each species consists of a population in interaction with the others, that reproduces and evolves in time. Each species is simultaneously a predator and a prey in a food chain. Mutations that change the interactions are supposed to occur randomly at a low rate. Extinctions of populations result naturally from the predator-prey dynamics. The model is not pinned in a fitness variable, and natural selection arises from the dynamics.

  4. La evaluación de la persistencia basada en una tarea (The assessment of persistence based on an acquisition-extinction learning task

    Directory of Open Access Journals (Sweden)

    José Manuel Hernández López

    2011-04-01

    Full Text Available The aim of the present study was to design an objective task to assess persistence as a personality variable. The conditions for assessing behavioral persistence were analyzed according to the concepts of motivational persistence, obstinate persistence and exploratory persistence. A free operant procedure with an acquisition and an extinction phase was used as a possible context for assessing persistence. The results show that the designed task enabled the measurement of the three variables of persistence in the sample studied. Internal consistency indexes were .928 for motivational persistence, .683 and .580 for the two indicators of obstinate persistence, and .905 for exploratory persistence. The relationships between each persistence variable and the initial motivation of the participants are consistent with those described in the literature.

  5. Differential Endocannabinoid Regulation of Extinction in Appetitive and Aversive Barnes Maze Tasks

    Science.gov (United States)

    Harloe, John P.; Thorpe, Andrew J.; Lichtman, Aron H.

    2008-01-01

    CB[subscript 1] receptor-compromised animals show profound deficits in extinguishing learned behavior from aversive conditioning tasks, but display normal extinction learning in appetitive operant tasks. However, it is difficult to discern whether the differential involvement of the endogenous cannabinoid system on extinction results from the…

  6. Inactivation of the Infralimbic but Not the Prelimbic Cortex Impairs Consolidation and Retrieval of Fear Extinction

    Science.gov (United States)

    Laurent, Vincent; Westbrook, R. Frederick

    2009-01-01

    Rats were subjected to one or two cycles of context fear conditioning and extinction to study the roles of the prelimbic cortex (PL) and infralimbic cortex (IL) in learning and relearning to inhibit fear responses. Inactivation of the PL depressed fear responses across the first or second extinction but did not impair learning or relearning fear…

  7. Ecology: Dynamics of Indirect Extinction.

    Science.gov (United States)

    Montoya, Jose M

    2015-12-01

    The experimental identification of the mechanism by which extinctions of predators trigger further predator extinctions emphasizes the role of indirect effects between species in disturbed ecosystems. It also has deep consequences for the hidden magnitude of the current biodiversity crisis.

  8. Learning, memory and long-term potentiation are altered in Nedd4 heterozygous mice.

    Science.gov (United States)

    Camera, Daria; Coleman, Harold A; Parkington, Helena C; Jenkins, Trisha A; Pow, David V; Boase, Natasha; Kumar, Sharad; Poronnik, Philip

    2016-04-15

    The consolidation of short-term memory into long-term memory involves changing protein level and activity for the synaptic plasticity required for long-term potentiation (LTP). AMPA receptor trafficking is a key determinant of LTP and recently ubiquitination by Nedd4 has been shown to play an important role via direct action on the GluA1 subunit, although the physiological relevance of these findings are yet to be determined. We therefore investigated learning and memory in Nedd4(+/-) mice that have a 50% reduction in levels of Nedd4. These mice showed decreased long-term spatial memory as evidenced by significant increases in the time taken to learn the location of and subsequently find a platform in the Morris water maze. In contrast, there were no significant differences between Nedd4(+/+) and Nedd4(+/-) mice in terms of short-term spatial memory in a Y-maze test. Nedd4(+/-) mice also displayed a significant reduction in post-synaptic LTP measured in hippocampal brain slices. Immunofluorescence of Nedd4 in the hippocampus confirmed its expression in hippocampal neurons of the CA1 region. These findings indicate that reducing Nedd4 protein by 50% significantly impairs LTP and long-term memory thereby demonstrating an important role for Nedd4 in these processes.

  9. Environmental impoverishment and aging alter object recognition, spatial learning, and dentate gyrus astrocytes.

    Science.gov (United States)

    Diniz, Daniel G; Foro, César A R; Rego, Carla M D; Gloria, David A; de Oliveira, Fabio R R; Paes, Juliana M P; de Sousa, Aline A; Tokuhashi, Tatyana P; Trindade, Lucas S; Turiel, Maíra C P; Vasconcelos, Erick G R; Torres, João B; Cunnigham, Colm; Perry, Victor H; Vasconcelos, Pedro F da Costa; Diniz, Cristovam W P

    2010-08-01

    Environmental and age-related effects on learning and memory were analysed and compared with changes observed in astrocyte laminar distribution in the dentate gyrus. Aged (20 months) and young (6 months) adult female albino Swiss mice were housed from weaning either in impoverished conditions or in enriched conditions, and tested for episodic-like and water maze spatial memories. After these behavioral tests, brain hippocampal sections were immunolabeled for glial fibrillary acid protein to identify astrocytes. The effects of environmental enrichment on episodic-like memory were not dependent on age, and may protect water maze spatial learning and memory from declines induced by aging or impoverished environment. In the dentate gyrus, the number of astrocytes increased with both aging and enriched environment in the molecular layer, increased only with aging in the polymorphic layer, and was unchanged in the granular layer. We suggest that long-term experience-induced glial plasticity by enriched environment may represent at least part of the circuitry groundwork for improvements in behavioral performance in the aged mice brain.

  10. Extinction and spontaneous recovery of spatial behavior in pigeons.

    Science.gov (United States)

    Leising, Kenneth J; Wong, Jared; Blaisdell, Aaron P

    2015-10-01

    We investigated extinction and spontaneous recovery of spatial associations using a landmark-based appetitive search task in a touchscreen preparation with pigeons. Four visual landmarks (A, B, C, and D) were separately established as signals of a hidden reinforced target among an 8 × 7 array of potential target locations. The target was located above landmarks (LM) A and C and below B and D. After conditioning, A and B were extinguished. Responding to A and C was assessed on probe tests 2 days following extinction, whereas, B and D were tested 14 days after extinction. We observed spontaneous recovery from spatial extinction following a 14-day, but not a 2-day, postextinction retention interval. Furthermore, by plotting the spatial distribution of responding across the X and Y axes during testing, we found that spontaneous recovery of responding to the target in our task was due to enhanced spatial control (i.e., a change in the overall distribution of responses) following the long delay to testing. These results add spatial extinction and spontaneous recovery to the list of findings supporting the assertion that extinction involves new learning that attenuates the originally acquired response, and that original learning of the spatial relationship between paired events survives extinction. (PsycINFO Database Record

  11. Mass Extinctions Past and Present.

    Science.gov (United States)

    Allmon, Warren Douglas

    1987-01-01

    Discusses some parallels that seem to exist between mass extinction recognizable in the geologic record and the impending extinction of a significant proportion of the earth's species due largely to tropical deforestation. Describes some recent theories of causal factors and periodicities in mass extinction. (Author/TW)

  12. Extinction of drug seeking: Neural circuits and approaches to augmentation.

    Science.gov (United States)

    McNally, Gavan P

    2014-01-01

    Extinction training can reduce drug seeking behavior. This article reviews the neural circuits that contribute to extinction and approaches to enhancing the efficacy of extinction. Extinction of drug seeking depends on cortical-striatal-hypothalamic and cortical-hypothalamic-thalamic pathways. These pathways interface, in the hypothalamus and thalamus respectively, with the neural circuits controlling reinstatement of drug seeking. The actions of these pathways at lateral hypothalamic orexin neurons, and of perifornical/dorsomedial hypothalamic derived opioid peptides at kappa opioid receptors in the paraventricular thalamus, are important for inhibiting drug seeking. Despite effectively reducing or inhibiting drug seeking in the short term, extinguished drug seeking is prone to relapse. Three different strategies to augment extinction learning or retrieval are reviewed: pharmacological augmentation, retrieval - extinction training, and provision of extinction memory retrieval cues. These strategies have been used in animal models and with human drug users to enhance extinction or cue exposure treatments. They hold promise as novel strategies to promote abstinence from drug seeking. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

  13. HDAC3-selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner.

    Science.gov (United States)

    Malvaez, Melissa; McQuown, Susan C; Rogge, George A; Astarabadi, Mariam; Jacques, Vincent; Carreiro, Samantha; Rusche, James R; Wood, Marcelo A

    2013-02-12

    Nonspecific histone deacetylase (HDAC) inhibition has been shown to facilitate the extinction of drug-seeking behavior in a manner resistant to reinstatement. A key open question is which specific HDAC is involved in the extinction of drug-seeking behavior. Using the selective HDAC3 inhibitor RGFP966, we investigated the role of HDAC3 in extinction and found that systemic treatment with RGFP966 facilitates extinction in mice in a manner resistant to reinstatement. We also investigated whether the facilitated extinction is related to the enhancement of extinction consolidation during extinction learning or to negative effects on performance or reconsolidation. These are key distinctions with regard to any compound being used to modulate extinction, because a more rapid decrease in a defined behavior is interpreted as facilitated extinction. Using an innovative combination of behavioral paradigms, we found that a single treatment of RGFP966 enhances extinction of a previously established cocaine-conditioned place preference, while simultaneously enhancing long-term object-location memory within subjects. During extinction consolidation, HDAC3 inhibition promotes a distinct pattern of histone acetylation linked to gene expression within the infralimbic cortex, hippocampus, and nucleus accumbens. Thus, the facilitated extinction of drug-seeking cannot be explained by adverse effects on performance. These results demonstrate that HDAC3 inhibition enhances the memory processes involved in extinction of drug-seeking behavior.

  14. Spatial learning in a virtual reality-based task is altered in very preterm children.

    Science.gov (United States)

    Cimadevilla, José M; Roldán, Lola; París, María; Arnedo, Marisa; Roldán, Susana

    2014-01-01

    Very preterm births prevent a complete development of the nervous system. The hippocampus is especially vulnerable in this population since the perinatal period is critical for its growth and development. Learning and memory abilities, like spatial memory, depend on the hippocampal integrity. In this study we applied virtual-reality-based tasks to assess spatial memory in a sample of 20 very preterm children of 7 and 8 years of age. Two different conditions of difficulty were used. Very preterm children performed poorly in the task in comparison with the control group. They committed more errors than controls searching for the rewarded positions. However, no significant differences were observed in the mean speed, an index of the motor abilities and joystick handling. These results suggest that the hippocampal function is affected in this sample. Nevertheless, other variables to consider are discussed.

  15. A mouse model of visual perceptual learning reveals alterations in neuronal coding and dendritic spine density in the visual cortex

    Directory of Open Access Journals (Sweden)

    Yan eWang

    2016-03-01

    Full Text Available Visual perceptual learning (VPL can improve spatial vision in normally sighted and visually impaired individuals. Although previous studies of humans and large animals have explored the neural basis of VPL, elucidation of the underlying cellular and molecular mechanisms remains a challenge. Owing to the advantages of molecular genetic and optogenetic manipulations, the mouse is a promising model for providing a mechanistic understanding of VPL. Here, we thoroughly evaluated the effects and properties of VPL on spatial vision in C57BL/6J mice using a two-alternative, forced-choice visual water task. Briefly, the mice underwent prolonged training at near the individual threshold of contrast or spatial frequency (SF for pattern discrimination or visual detection for 35 consecutive days. Following training, the contrast-threshold trained mice showed an 87% improvement in contrast sensitivity (CS and a 55% gain in visual acuity (VA. Similarly, the SF-threshold trained mice exhibited comparable and long-lasting improvements in VA and significant gains in CS over a wide range of SFs. Furthermore, learning largely transferred across eyes and stimulus orientations. Interestingly, learning could transfer from a pattern discrimination task to a visual detection task, but not vice versa. We validated that this VPL fully restored VA in adult amblyopic mice and old mice. Taken together, these data indicate that mice, as a species, exhibit reliable VPL. Intrinsic signal optical imaging revealed that mice with perceptual training had higher cut-off SFs in primary visual cortex (V1 than those without perceptual training. Moreover, perceptual training induced an increase in the dendritic spine density in layer 2/3 pyramidal neurons of V1. These results indicated functional and structural alterations in V1 during VPL. Overall, our VPL mouse model will provide a platform for investigating the neurobiological basis of VPL.

  16. Effects of altered loading states on muscle plasticity: what have we learned from rodents?

    Science.gov (United States)

    Baldwin, K. M.

    1996-01-01

    This paper summarizes the key findings concerning the adaptive properties of rodent muscle in response to altered loading states. When the mechanical stress on the muscle is chronically increased, the muscle adapts by hypertrophying its fibers. This response is regulated by processes resulting in contractile protein expression reflecting slower phenotypes, thereby enabling the muscle to better support load-hearing activity. In contrast, reducing the load-bearing activity induces an opposite response whereby muscles used for both antigravity function and locomotion atrophy while transforming some of the slow fibers into faster contractile phenotypes. Accompanying the atrophy is both a reduced power generating and activity sustaining capability. These adaptive processes are regulated by both transcriptional and translational processes. Available evidence further suggests that the interaction of heavy resistance activity and hormonal/growth factors (insulin-like growth factor, growth hormone, glucocorticoids, etc.) are critical in the maintenance of muscle mass and function. Also resistance training, in contrast to other activities such as endurance running, provides a more economical form of stress because less mechanical activity is required to maintain muscle homeostasis in the context of chronic states of weightlessness.

  17. Histone Modifications around Individual BDNF Gene Promoters in Prefrontal Cortex Are Associated with Extinction of Conditioned Fear

    Science.gov (United States)

    Bredy, Timothy W.; Wu, Hao; Crego, Cortney; Zellhoefer, Jessica; Sun, Yi E.; Barad, Mark

    2007-01-01

    Extinction of conditioned fear is an important model both of inhibitory learning and of behavior therapy for human anxiety disorders. Like other forms of learning, extinction learning is long-lasting and depends on regulated gene expression. Epigenetic mechanisms make an important contribution to persistent changes in gene expression; therefore,…

  18. Yohimbine Impairs Extinction of Cocaine-Conditioned Place Preference in an [alpha] [subscript 2]-Adrenergic Receptor Independent Process

    Science.gov (United States)

    Davis, Adeola R.; Shields, Angela D.; Brigman, Jonathan L.; Norcross, Maxine; McElligott, Zoe A.; Holmes, Andrew; Winder, Danny G.

    2008-01-01

    Extinction, a form of learning that has the ability to reshape learned behavior based on new experiences, has been heavily studied utilizing fear learning paradigms. Mechanisms underlying extinction of positive-valence associations, such as drug self-administration and place preference, are poorly understood yet may have important relevance to…

  19. Stressor controllability modulates fear extinction in humans.

    Science.gov (United States)

    Hartley, Catherine A; Gorun, Alyson; Reddan, Marianne C; Ramirez, Franchesca; Phelps, Elizabeth A

    2014-09-01

    Traumatic events are proposed to play a role in the development of anxiety disorders, however not all individuals exposed to extreme stress experience a pathological increase in fear. Recent studies in animal models suggest that the degree to which one is able to control an aversive experience is a critical factor determining its behavioral consequences. In this study, we examined whether stressor controllability modulates subsequent conditioned fear expression in humans. Participants were randomly assigned to an escapable stressor condition, a yoked inescapable stressor condition, or a control condition involving no stress exposure. One week later, all participants underwent fear conditioning, fear extinction, and a test of extinction retrieval the following day. Participants exposed to inescapable stress showed impaired fear extinction learning and increased fear expression the following day. In contrast, escapable stress improved fear extinction and prevented the spontaneous recovery of fear. Consistent with the bidirectional controllability effects previously reported in animal models, these results suggest that one's degree of control over aversive experiences may be an important factor influencing the development of psychological resilience or vulnerability in humans.

  20. Contextual-Specificity of Short-Delay Extinction in Humans: Renewal of Fear-Potentiated Startle in a Virtual Environment

    Science.gov (United States)

    Alvarez, Ruben P.; Johnson, Linda; Grillon, Christian

    2007-01-01

    A recent fear-potentiated startle study in rodents suggested that extinction was not context dependent when extinction was conducted after a short delay following acquisition, suggesting that extinction can lead to erasure of fear learning in some circumstances. The main objective of this study was to attempt to replicate these findings in humans…

  1. Extinction cascades partially estimate herbivore losses in a complete Lepidoptera--plant food web.

    Science.gov (United States)

    Pearse, Ian S; Altermatt, Florian

    2013-08-01

    The loss of species from an ecological community can have cascading effects leading to the extinction of other species. Specialist herbivores are highly diverse and may be particularly susceptible to extinction due to host plant loss. We used a bipartite food web of 900 Lepidoptera (butterfly and moth) herbivores and 2403 plant species from Central Europe to simulate the cascading effect of plant extinctions on Lepidoptera extinctions. Realistic extinction sequences of plants, incorporating red-list status, range size, and native status, altered subsequent Lepidoptera extinctions. We compared simulated Lepidoptera extinctions to the number of actual regional Lepidoptera extinctions and found that all predicted scenarios underestimated total observed extinctions but accurately predicted observed extinctions attributed to host loss (n = 8, 14%). Likely, many regional Lepidoptera extinctions occurred for reasons other than loss of host plant alone, such as climate change and habitat loss. Ecological networks can be useful in assessing a component of extinction risk to herbivores based on host loss, but further factors may be equally important.

  2. Spontaneous recovery from extinction in the infant rat.

    Science.gov (United States)

    Revillo, D A; Paglini, M G; Arias, C

    2014-11-01

    Within the Pavlovian conditioning framework, extinction is a procedure in which, after conditioning, the conditioned stimulus (CS) is repeatedly presented without the unconditioned stimulus (US). During this procedure the conditioned response (CR) is gradually attenuated. It has been suggested that extinction during the early stages of ontogeny is a qualitatively different process from extinction in adulthood: during infancy, extinction may result in erasure of the memory, while during adulthood extinction involves new learning. This conclusion was supported by studies showing that renewal, reinstatement or spontaneous recovery procedures were not effective during infancy for recovering the CR once it had been extinguished. These studies used the freezing response as the only behavioral index, although some recent evidence indicates that the absence of freezing after conditioning or after extinction does not necessarily imply a deficit in memory, and that other behavioral indexes may be more sensitive to detecting conditioning effects. The goal of the present study was to analyze extinction in preweanling rats by examining the possibility of the spontaneous recovery of a conditioned fear response, measured through a different set of mutually-exclusive behaviors that constitute an exhaustive ethogram, and including control groups (Experiment 1: US-Only and CS-Only; Experiment 2: US-Only, CS-Only and Unpaired) in order to examine whether non-associative learning may explain quantitative or qualitative changes in the frequency of specific responses during extinction or recovery. Extinction produced changes in the expression of freezing, grooming and exploration, and the clearest evidence of spontaneous recovery came from the analysis of freezing behavior. The pattern of behavior observed during extinction is compatible with theoretical approaches which consider different dynamic behavioral systems, and it also fit in well with a molar approach to the analysis of

  3. A theoretical quantitative genetic study of negative ecological interactions and extinction times in changing environments

    OpenAIRE

    Jones Adam G

    2008-01-01

    Abstract Background Rapid human-induced changes in the environment at local, regional and global scales appear to be contributing to population declines and extinctions, resulting in an unprecedented biodiversity crisis. Although in the short term populations can respond ecologically to environmental alterations, in the face of persistent change populations must evolve or become extinct. Existing models of evolution and extinction in changing environments focus only on single species, even th...

  4. Maternal chewing during prenatal stress ameliorates stress-induced hypomyelination, synaptic alterations, and learning impairment in mouse offspring.

    Science.gov (United States)

    Suzuki, Ayumi; Iinuma, Mitsuo; Hayashi, Sakurako; Sato, Yuichi; Azuma, Kagaku; Kubo, Kin-Ya

    2016-11-15

    Maternal chewing during prenatal stress attenuates both the development of stress-induced learning deficits and decreased cell proliferation in mouse hippocampal dentate gyrus. Hippocampal myelination affects spatial memory and the synaptic structure is a key mediator of neuronal communication. We investigated whether maternal chewing during prenatal stress ameliorates stress-induced alterations of hippocampal myelin and synapses, and impaired development of spatial memory in adult offspring. Pregnant mice were divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube, and was initiated on day 12 of pregnancy and continued until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint. In 1-month-old pups, spatial memory was assessed in the Morris water maze, and hippocampal oligodendrocytes and synapses in CA1 were assayed by immunohistochemistry and electron microscopy. Prenatal stress led to impaired learning ability, and decreased immunoreactivity of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampal CA1 in adult offspring. Numerous myelin sheath abnormalities were observed. The G-ratio [axonal diameter to axonal fiber diameter (axon plus myelin sheath)] was increased and postsynaptic density length was decreased in the hippocampal CA1 region. Maternal chewing during stress attenuated the prenatal stress-induced impairment of spatial memory, and the decreased MBP and CNPase immunoreactivity, increased G-ratios, and decreased postsynaptic-density length in the hippocampal CA1 region. These findings suggest that chewing during prenatal stress in dams could be an effective coping strategy to prevent hippocampal behavioral and morphologic impairments in their offspring.

  5. Interactions of time of day and sleep with between-session habituation and extinction memory in young adult males

    OpenAIRE

    Pace-Schott, Edward F.; Tracy, Lauren E.; Rubin, Zoe; Mollica, Adrian G.; Jeffrey M Ellenbogen; Bianchi, Matt T.; Milad, Mohammed R.; Pitman, roger k; Orr, Scott P

    2014-01-01

    Within-session habituation and extinction learning co-occur as do subsequent consolidation of habituation (i.e., between-session habituation) and extinction memory. We sought to determine if, as we predicted: (1) between-session habituation is greater across a night of sleep vs. a day awake; (2) time-of-day accounts for differences; (3) between-session habituation predicts consolidation of extinction memory; (4) sleep predicts between-session habituation and/or extinction memory. Participants...

  6. THE MEMORY SYSTEM ENGAGED DURING ACQUISITION DETERMINES THE EFFECTIVENESS OF DIFFERENT EXTINCTION PROTOCOLS

    Directory of Open Access Journals (Sweden)

    Jarid eGoodman

    2015-11-01

    Full Text Available Previous research indicates that extinction of rodent maze behavior may occur without explicit performance of the previously required response. In latent extinction, confining an animal to a previously rewarded goal location without reinforcement is typically sufficient to produce extinction of maze learning. However, previous studies have not determined whether latent extinction may be successfully employed to extinguish all types of memory acquired in the maze, or whether only specific types of memory may be vulnerable to latent extinction. The present study examined whether latent extinction may be effective across two plus-maze tasks that depend on anatomically distinct neural systems. Adult male Long-Evans rats were trained in a hippocampus-dependent place learning task (experiment 1, in which animals were trained to approach a consistent spatial location for food reward. A separate group of rats were trained in a dorsolateral striatum-dependent response learning task (experiment 2, in which animals were trained to make a consistent egocentric body-turn response for food reward. Following training, animals received response extinction or latent extinction. For response extinction, animals were given the opportunity to execute the original running approach response toward the empty food cup. For latent extinction, animals were confined to the original goal locations with the empty food cup, thus preventing them from making the original running approach response. Results indicate that, relative to no extinction, latent extinction was effective at extinguishing memory in the place learning task, but remained ineffective in the response learning task. In contrast, typical response extinction remained very effective at extinguishing memory in both place and response learning tasks. The present findings confirm that extinction of maze learning may occur with or without overt performance of the previously acquired response, but that the

  7. Taste-immunosuppression engram: reinforcement and extinction.

    Science.gov (United States)

    Niemi, Maj-Britt; Härting, Margarete; Kou, Wei; Del Rey, Adriana; Besedovsky, Hugo O; Schedlowski, Manfred; Pacheco-López, Gustavo

    2007-08-01

    Several Pavlovian conditioning paradigms have documented the brain's abilities to sense immune-derived signals or immune status, associate them with concurrently relevant extereoceptive stimuli, and reinstate such immune responses on demand. Specifically, the naturalistic relation of food ingestion with its possible immune consequences facilitates taste-immune associations. Here we demonstrate that the saccharin taste can be associated with the immunosuppressive agent cyclosporine A, and that such taste-immune associative learning is subject to reinforcement. Furthermore, once consolidated, this saccharin-immunosuppression engram is resistant to extinction when avoidance behavior is assessed. More importantly, the more this engram is activated, either at association or extinction phases, the more pronounced is the conditioned immunosuppression.

  8. Extinction Events Can Accelerate Evolution

    DEFF Research Database (Denmark)

    Lehman, Joel; Miikkulainen, Risto

    2015-01-01

    computational support for this hypothesis, this paper shows how increased evolvability will result from simulated extinction events in two computational models of evolved behavior. The conclusion is that although they are destructive in the short term, extinction events may make evolution more prolific......Extinction events impact the trajectory of biological evolution significantly. They are often viewed as upheavals to the evolutionary process. In contrast, this paper supports the hypothesis that although they are unpredictably destructive, extinction events may in the long term accelerate...... evolution by increasing evolvability. In particular, if extinction events extinguish indiscriminately many ways of life, indirectly they may select for the ability to expand rapidly through vacated niches. Lineages with such an ability are more likely to persist through multiple extinctions. Lending...

  9. Extinction events can accelerate evolution.

    Directory of Open Access Journals (Sweden)

    Joel Lehman

    Full Text Available Extinction events impact the trajectory of biological evolution significantly. They are often viewed as upheavals to the evolutionary process. In contrast, this paper supports the hypothesis that although they are unpredictably destructive, extinction events may in the long term accelerate evolution by increasing evolvability. In particular, if extinction events extinguish indiscriminately many ways of life, indirectly they may select for the ability to expand rapidly through vacated niches. Lineages with such an ability are more likely to persist through multiple extinctions. Lending computational support for this hypothesis, this paper shows how increased evolvability will result from simulated extinction events in two computational models of evolved behavior. The conclusion is that although they are destructive in the short term, extinction events may make evolution more prolific in the long term.

  10. Extinction Events Can Accelerate Evolution

    Science.gov (United States)

    Lehman, Joel; Miikkulainen, Risto

    2015-01-01

    Extinction events impact the trajectory of biological evolution significantly. They are often viewed as upheavals to the evolutionary process. In contrast, this paper supports the hypothesis that although they are unpredictably destructive, extinction events may in the long term accelerate evolution by increasing evolvability. In particular, if extinction events extinguish indiscriminately many ways of life, indirectly they may select for the ability to expand rapidly through vacated niches. Lineages with such an ability are more likely to persist through multiple extinctions. Lending computational support for this hypothesis, this paper shows how increased evolvability will result from simulated extinction events in two computational models of evolved behavior. The conclusion is that although they are destructive in the short term, extinction events may make evolution more prolific in the long term. PMID:26266804

  11. Activation of prefrontal cortical parvalbumin interneurons facilitates extinction of reward-seeking behavior.

    Science.gov (United States)

    Sparta, Dennis R; Hovelsø, Nanna; Mason, Alex O; Kantak, Pranish A; Ung, Randall L; Decot, Heather K; Stuber, Garret D

    2014-03-05

    Forming and breaking associations between emotionally salient environmental stimuli and rewarding or aversive outcomes is an essential component of learned adaptive behavior. Importantly, when cue-reward contingencies degrade, animals must exhibit behavioral flexibility to extinguish prior learned associations. Understanding the specific neural circuit mechanisms that operate during the formation and extinction of conditioned behaviors is critical because dysregulation of these neural processes is hypothesized to underlie many of the maladaptive and pathological behaviors observed in various neuropsychiatric disorders in humans. The medial prefrontal cortex (mPFC) participates in the behavioral adaptations seen in both appetitive and aversive-cue-mediated responding, but the precise cell types and circuit mechanisms sufficient for driving these complex behavioral states remain largely unspecified. Here, we recorded and manipulated the activity of parvalbumin-positive fast spiking interneurons (PV+ FSIs) in the prelimbic area (PrL) of the mPFC in mice. In vivo photostimulation of PV+ FSIs resulted in a net inhibition of PrL neurons, providing a circuit blueprint for behavioral manipulations. Photostimulation of mPFC PV+ cells did not alter anticipatory or consummatory licking behavior during reinforced training sessions. However, optical activation of these inhibitory interneurons to cues associated with reward significantly accelerated the extinction of behavior during non-reinforced test sessions. These data suggest that suppression of excitatory mPFC networks via increased activity of PV+ FSIs may enhance reward-related behavioral flexibility.

  12. High extinction amplitude modulation in ultrashort pulse shaping

    CERN Document Server

    Lin, Yen-Wei

    2016-01-01

    We explored the issues related to the resolution and the modulation extinction when filtering the spectrum of a UV femtosecond laser with a standard ultrashort pulse shaper. We have learned that a higher pulse shaping resolution often requires a larger working beam size or a higher density grating for greater dispersion. However, these approaches also introduce more optical errors and degrade the extinction. In this work, we examined specifics of each component to determine the best configuration of our spectral filtering setup. As a proof-of-concept demonstration, we utilized elements available as standard products and achieved 100 GHz filtering resolution with high extinction at the UV-A wavelength, which is superb in this wavelength range. The high extinction spectral filtering is especially important while modifying a broadband laser for the optical control of molecule's internal state.

  13. Extinction and retrieval+extinction of conditioned fear differentially activate medial prefrontal cortex and amygdala in rats

    Directory of Open Access Journals (Sweden)

    Hongjoo Joanne Lee

    2016-01-01

    Full Text Available Pairing a previously neutral conditioned stimulus (CS; e.g., a tone to an aversive unconditioned stimulus (US; e.g., a footshock leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing. We have previously shown that an extinction session that occurs within the reconsolidation window (termed retrieval+extinction attenuates fear responding and prevents the return of fear in Pavlovian fear conditioning (Monfils et al., 2009. To date, the mechanisms that explain the different behavioral outcomes between standard extinction and retrieval+extinction remain poorly understood. Here we sought to examine the differential temporal engagement of specific neural systems by these 2 approaches using Arc catFISH (cellular compartment analysis of temporal activity using fluorescence in situ hybridization. Our results demonstrate that extinction and retrieval+extinction lead to differential patterns of expression, suggesting that they engage different networks. These findings provide insight into the neural mechanisms that allow extinction during reconsolidation to prevent the return of fear in rats.

  14. Glutamate Receptors in Extinction and Extinction-Based Therapies for Psychiatric Illness

    OpenAIRE

    Myers, Karyn M.; William A Carlezon; Davis, Michael

    2010-01-01

    Some psychiatric illnesses involve a learned component. For example, in posttraumatic stress disorder, memories triggered by trauma-associated cues trigger fear and anxiety, and in addiction, drug-associated cues elicit drug craving and withdrawal. Clinical interventions to reduce the impact of conditioned cues in eliciting these maladaptive conditioned responses are likely to be beneficial. Extinction is a method of lessening conditioned responses and involves repeated exposures to a cue in ...

  15. Extinction under a Behavioral Microscope: Isolating the Sources of Decline in Operant Response Rate

    OpenAIRE

    Cheung, Timothy H. C.; Neisewander, Janet L.; Sanabria, Federico

    2012-01-01

    Extinction performance is often used to assess underlying psychological processes without the interference of reinforcement. For example, in the extinction/reinstatement paradigm, motivation to seek drug is assessed by measuring responding elicited by drug-associated cues without drug reinforcement. Nonetheless, extinction performance is governed by several psychological processes that involve motivation, memory, learning, and motoric functions. These processes are confounded when overall res...

  16. Regulation of extinction-related plasticity by opioid receptors in the ventrolateral periaqueductal gray matter

    Directory of Open Access Journals (Sweden)

    Ryan Parsons

    2010-08-01

    Full Text Available Recent work has led to a better understanding of the neural mechanisms underlying the extinction of Pavlovian fear conditioning. Long-term synaptic changes in the medial prefrontal cortex (mPFC are critical for extinction learning, but very little is currently known about how the mPFC and other brain areas interact during extinction. The current study examined the effect of drugs that impair the extinction of fear conditioning on the activation of the extracellular-related kinase/mitogen-activated protein kinase (ERK/MAPK in brain regions that likely participate in the consolidation of extinction learning. Inhibitors of opioid and N-methyl-D-aspartic acid (NMDA receptors were applied to the ventrolateral periaqueductal gray matter (vlPAG and amygdala shortly before extinction training. Results from these experiments show that blocking opioid receptors in the vlPAG prevented the formation of extinction memory, whereas NMDA receptor blockade had no effect. Conversely, blocking NMDA receptors in the amygdala disrupted the formation of fear extinction memory, but opioid receptor blockade in the same brain area did not. Subsequent experiments tested the effect of these drug treatments on the activation of the ERK/MAPK signaling pathway in various brain regions following extinction training. Only opioid receptor blockade in the vlPAG disrupted ERK phosphorylation in the mPFC and amygdala. These data support the idea that opiodergic signaling derived from the vlPAG affects plasticity across the brain circuit responsible for the formation of extinction memory.

  17. Postretrieval Extinction in Adolescence Prevents Return of Juvenile Fear

    Science.gov (United States)

    Jones, Carolyn E.; Monfils, Marie-H.

    2016-01-01

    Traumatic experiences early in life can contribute to the development of mood and anxiety disorders that manifest during adolescence and young adulthood. In young rats exposed to acute fear or stress, alterations in neural development can lead to enduring behavioral abnormalities. Here, we used a modified extinction intervention…

  18. The effects of compound stimulus extinction and inhibition of noradrenaline reuptake on the renewal of alcohol seeking

    Science.gov (United States)

    Furlong, T M; Pan, M J; Corbit, L H

    2015-01-01

    Alcohol-related stimuli can trigger relapse of alcohol-seeking behaviors even after extended periods of abstinence. Extinction of such stimuli can reduce their impact on relapse; however, the expression of extinction can be disrupted when testing occurs outside the context where extinction learning took place, an effect termed renewal. Behavioral and pharmacological methods have recently been shown to augment extinction learning; yet, it is not known whether the improved expression of extinction following these treatments remains context-dependent. Here we examined whether two methods, compound–stimulus extinction and treatment with the noradrenaline reuptake inhibitor atomoxetine, would reduce the vulnerability of extinction to a change in context. Following alcohol self-administration, responding was extinguished in a distinct context. After initial extinction, further extinction was given to a target stimulus presented in compound with another alcohol-predictive stimulus intended to augment prediction error (Experiment 1) or after a systemic injection of atomoxetine (1.0 mg kg−1; Experiment 2). A stimulus extinguished as part of a compound elicited less responding than a stimulus receiving equal extinction alone regardless of whether animals were tested in the training or extinction context; however, reliable renewal was not observed in this paradigm. Importantly, atomoxetine enhanced extinction relative to controls even in the presence of a reliable renewal effect. Thus, extinction of alcohol-seeking behavior can be improved by extinguishing multiple alcohol-predictive stimuli or enhancing noradrenaline neurotransmission during extinction training. Importantly, both methods improve extinction even when the context is changed between extinction training and test, and thus could be utilized to enhance the outcome of extinction-based treatments for alcohol-use disorders. PMID:26327688

  19. Fear extinction can be made state-dependent on peripheral epinephrine: role of norepinephrine in the nucleus tractus solitarius.

    Science.gov (United States)

    Rosa, Jessica; Myskiw, Jociane C; Furini, Cristiane R G; Sapiras, Gerson G; Izquierdo, Ivan

    2014-09-01

    We investigate whether the extinction of inhibitory avoidance (IA) learning can be subjected to endogenous state-dependence with systemic injections of epinephrine (E), and whether endogenous norepinephrine (NE) and the nucleus tractus solitarius (NTS)→locus coeruleus→hippocampus/amygdala (HIPP/BLA) pathway participate in this. Rats trained in IA were submitted to two sessions of extinction 24 h apart: In the first, the animals were submitted to a training session of extinction, and in the second they were tested for the retention of extinction. Saline or E were given i.p. immediately after the extinction training (post-extinction training injections) and/or 6 min before the extinction test (pre-extinction test). Post-extinction training E (50 or 100 μg/kg) induced a poor retrieval of extinction in the test session of this task unless an additional E injection (50 μg/kg) was given prior to the extinction test. This suggested state-dependence. Muscimol (0.01 μg/side) microinfused into the NTS prior to the extinction test session blocked E-induced state-dependence. Norepinephrine (NE, 1 μg/side) infused bilaterally into NTS restores the extinction impairment caused by post-extinction training i.p. E. In animals with bilateral NTS blockade induced by muscimol, NE (1 μg/side) given prior to the extinction test into the CA1 region of the dorsal hippocampus or into the basolateral amygdala restored the normal extinction levels that had been impaired by muscimol. These results suggest a role for the NTS→locus coeruleus→HIPP/BLA pathway in the retrieval of extinction, as it has been shown to have in the consolidation of inhibitory avoidance and of object recognition learning.

  20. Exploring co-extinction correlates

    DEFF Research Database (Denmark)

    Carpaneto, Giuseppe Maria; Mazziotta, Adriano; Pittino, Riccardo

    2011-01-01

    Co-extinction is a recurring topic in conservation biology. Quantification of co-extinction has been generally restricted to parasite-host, predator-prey and herbivore-host plant interactions. The loss of detritivorous insects upon the depletion of herbivore mammals has been poorly explored. Here...

  1. Extinction debt on oceanic islands

    DEFF Research Database (Denmark)

    Triantis, Kostas A.; Borges, Paulo A. V.; Ladle, Richard J.

    2010-01-01

    Habitat destruction is the leading cause of species extinctions. However, there is typically a time-lag between the reduction in habitat area and the eventual disappearance of the remnant populations. These "surviving but ultimately doomed" species represent an extinction debt. Calculating the ma...

  2. Extinction retention predicts improvement in social anxiety symptoms following exposure therapy

    NARCIS (Netherlands)

    Berry, A.C.; Rosenfield, D.; Smits, J.A.J.

    2009-01-01

    Background: Several researchers have argued that basic research oil extinction learning can guide efforts to enhance the efficacy of exposure-based therapy. At the basis of this translational research paradigm is the assumption that extinction retention is important to the outcome of exposure-based

  3. Reexposure to the Amnestic Agent Alleviates Cycloheximide-Induced Retrograde Amnesia for Reactivated and Extinction Memories

    Science.gov (United States)

    Briggs, James F.; Olson, Brian P.

    2013-01-01

    We investigated whether reexposure to an amnestic agent would reverse amnesia for extinction of learned fear similar to that of a reactivated memory. When cycloheximide (CHX) was administered immediately after a brief cue-induced memory reactivation (15 sec) and an extended extinction session (12 min) rats showed retrograde amnesia for both…

  4. The Role of the Medial Prefrontal Cortex in Trace Fear Extinction

    Science.gov (United States)

    Kwapis, Janine L.; Jarome, Timothy J.; Helmstetter, Fred J.

    2015-01-01

    The extinction of delay fear conditioning relies on a neural circuit that has received much attention and is relatively well defined. Whether this established circuit also supports the extinction of more complex associations, however, is unclear. Trace fear conditioning is a better model of complex relational learning, yet the circuit that…

  5. Extinction, Reacquisition, and Rapid Forgetting of Eyeblink Conditioning in Developing Rats

    Science.gov (United States)

    Brown, Kevin L.; Freeman, John H.

    2014-01-01

    Eyeblink conditioning is a well-established model for studying the developmental neurobiology of associative learning and memory. However, age differences in extinction and subsequent reacquisition have yet to be studied using this model. The present study examined extinction and reacquisition of eyeblink conditioning in developing rats. In…

  6. Selective and Protracted Effect of Nifedipine on Fear Memory Extinction Correlates with Induced Stress Response

    Science.gov (United States)

    Waltereit, Robert; Mannhardt, Sonke; Nescholta, Sabine; Maser-Gluth, Christiane; Bartsch, Dusan

    2008-01-01

    Memory extinction, defined as a decrease of a conditioned response as a function of a non-reinforced conditioned stimulus presentation, has high biological and clinical relevance. Extinction is not a passive reversing or erasing of the plasticity associated with acquisition, but a novel, active learning process. Nifedipine blocks L-type voltage…

  7. Hubble Tarantula Treasury Project. IV. The extinction law

    CERN Document Server

    De Marchi, Guido; Sabbi, Elena; Lennon, Daniel; Anderson, Jay; van der Marel, Roeland; Cignoni, Michele; Grebel, Eva K; Larsen, Soeren; Zaritsky, Dennis; Zeidler, Peter; Gouliermis, Dimitrios; Aloisi, Alessandra

    2015-01-01

    We report on the study of interstellar extinction across the Tarantula nebula (30 Doradus), in the Large Magellanic Cloud, using observations from the Hubble Tarantula Treasury Project in the 0.3 - 1.6 micron range. The considerable and patchy extinction inside the nebula causes about 3500 red clump stars to be scattered along the reddening vector in the colour-magnitude diagrams, thereby allowing an accurate determination of the reddening slope in all bands. The measured slope of the reddening vector is remarkably steeper in all bands than in the the Galactic diffuse interstellar medium. At optical wavelengths, the larger ratio of total-to-selective extinction, namely Rv = 4.5 +/- 0.2, implies the presence of a grey component in the extinction law, due to a larger fraction of large grains. The extra large grains are most likely ices from supernova ejecta and will significantly alter the extinction properties of the region until they sublimate in 50 - 100 Myr. We discuss the implications of this extinction la...

  8. Hubble Tarantula Treasury Project - IV. The extinction law

    Science.gov (United States)

    De Marchi, Guido; Panagia, Nino; Sabbi, Elena; Lennon, Daniel; Anderson, Jay; van der Marel, Roeland; Cignoni, Michele; Grebel, Eva K.; Larsen, Søren; Zaritsky, Dennis; Zeidler, Peter; Gouliermis, Dimitrios; Aloisi, Alessandra

    2016-02-01

    We report on the study of interstellar extinction across the Tarantula Nebula (30 Doradus), in the Large Magellanic Cloud, using observations from the Hubble Tarantula Treasury Project in the 0.3-1.6 μm range. The considerable and patchy extinction inside the nebula causes about 3500 red clump stars to be scattered along the reddening vector in the colour-magnitude diagrams, thereby allowing an accurate determination of the reddening slope in all bands. The measured slope of the reddening vector is remarkably steeper in all bands than in the the Galactic diffuse interstellar medium. At optical wavelengths, the larger ratio of total-to-selective extinction, namely RV = 4.5 ± 0.2, implies the presence of a grey component in the extinction law, due to a larger fraction of large grains. The extra large grains are most likely ices from supernova ejecta and will significantly alter the extinction properties of the region until they sublimate in 50-100 Myr. We discuss the implications of this extinction law for the Tarantula Nebula and in general for regions of massive star formation in galaxies. Our results suggest that fluxes of strongly star-forming regions are likely to be underestimated by a factor of about 2 in the optical.

  9. Measuring Extinction with ALE

    Science.gov (United States)

    Zimmer, Peter C.; McGraw, J. T.; Gimmestad, G. G.; Roberts, D.; Stewart, J.; Smith, J.; Fitch, J.

    2007-12-01

    ALE (Astronomical LIDAR for Extinction) is deployed at the University of New Mexico's (UNM) Campus Observatory in Albuquerque, NM. It has begun a year-long testing phase prior deployment at McDonald Observatory in support of the CCD/Transit Instrument II (CTI-II). ALE is designed to produce a high-precision measurement of atmospheric absorption and scattering above the observatory site every ten minutes of every moderately clear night. LIDAR (LIght Detection And Ranging) is the VIS/UV/IR analog of radar, using a laser, telescope and time-gated photodetector instead of a radio transmitter, dish and receiver. In the case of ALE -- an elastic backscatter LIDAR -- 20ns-long, eye-safe laser pulses are launched 2500 times per second from a 0.32m transmitting telescope co-mounted with a 50mm short-range receiver on an alt-az mounted 0.67m long-range receiver. Photons from the laser pulse are scattered and absorbed as the pulse propagates through the atmosphere, a portion of which are scattered into the field of view of the short- and long-range receiver telescopes and detected by a photomultiplier. The properties of a given volume of atmosphere along the LIDAR path are inferred from both the altitude-resolved backscatter signal as well as the attenuation of backscatter signal from altitudes above it. We present ALE profiles from the commissioning phase and demonstrate some of the astronomically interesting atmospheric information that can be gleaned from these data, including, but not limited to, total line-of-sight extinction. This project is funded by NSF Grant 0421087.

  10. The end-Permian mass extinction: A complex, multicausal extinction

    Science.gov (United States)

    Erwin, D. H.

    1994-01-01

    The end-Permian mass extinction was the most extensive in the history of life and remains one of the most complex. Understanding its causes is particularly important because it anchors the putative 26-m.y. pattern of periodic extinction. However, there is no good evidence for an impact and this extinction appears to be more complex than others, involving at least three phases. The first began with the onset of a marine regression during the Late Permian and resulting elimination of most marine basins, reduction in habitat area, and increased climatic instability; the first pulse of tetrapod extinctions occurred in South Africa at this time. The second phase involved increased regression in many areas (although apparently not in South China) and heightened climatic instability and environmental degradation. Release of gas hydrates, oxidation of marine carbon, and the eruption of the Siberian flood basalts occurred during this phase. The final phase of the extinction episode began with the earliest Triassic marine regression and destruction of nearshore continental habitats. Some evidence suggests oceanic anoxia may have developed during the final phase of the extinction, although it appears to have been insufficient to the sole cause of the extinction.

  11. Functional Extinctions of Species in Ecological Networks

    OpenAIRE

    Säterberg, Torbjörn

    2016-01-01

    Current rates of extinctions are estimated to be around 1000 times higher than background rates that would occur without anthropogenic impacts. These extinction rates refer to the traditional view of extinctions, i.e. numerical extinctions. This thesis is about another type of extinctions: functional extinctions. Those occur when the abundance of a species is too small to uphold the species’ ecologically interactive role. I have taken a theoretical approach and used dynamical models to invest...

  12. Extinction Laws toward Stellar Sources within a Dusty Circimstellar Medium and Implications for Type Ia Supernovae

    CERN Document Server

    Nagao, T; Nozawa, T

    2016-01-01

    Many astronomical objects are surrounded by dusty environments. In such dusty objects, multiple scattering processes of photons by circumstellar (CS) dust grains can effectively alter extinction properties. In this paper, we systematically investigate effects of multiple scattering on extinction laws for steady-emission sources surrounded by the dusty CS medium, using a radiation transfer simulation based on the Monte Carlo technique. In particular, we focus on whether and how the extinction properties are affected by properties of CS dust grains, adopting various dust grain models. We {\\bf confirm} that behaviors of the (effective) extinction laws are highly dependent on the properties of CS grains. Especially, the total-to-selective extinction ratio $R_{V}$, which characterizes the extinction law, can be either increased or decreased, compared to the case without multiple scattering. We find that the criterion for this behavior is given by a ratio of albedos in the $B$ and $V$ bands. We also find that eithe...

  13. Infant Contingency/Extinction Performance after Observing Partial Reinforcement

    Science.gov (United States)

    Weir, Catherine; Toland, Cynthia; King, Rose Ann; Martin, Lisa Maas

    2005-01-01

    Social information gathering by infants 6 and 12 months old was examined as a foundation for later social learning that may be uniquely human. Infant performance on a contingency/extinction task was studied following a caregiver demonstration of the contingency on varied reinforcement schedules. Infants who observed caregivers receive any…

  14. The effect of morphine on fear extinction in rats.

    Science.gov (United States)

    Morris, M D; Gebhart, G F

    1978-05-31

    Rats were trained on an appetitive discretetrial discriminated-punishment task in which they learned to suppress responding when an intense flashing light predicting punishment was present and to respond rapidly on trials when the flashing light was absent. Once animals were performing discriminatively, 0.75, 3.0, or 6.0 mg/kg of morphine (base) was administered and a fear extinction session consisting of 60 nonshocked presentations of the flashing light was given. Two saline control groups, one that received fear extinction and one that did not, were also included in the experiment. On the day following fear extinction, all rats were tested in the undrugged state on the discriminated punishment problem, but without shock. The rats receiving 3.0 and 6.0 mg/kg of morphine before the fear extinction session were suppressed by the flashing light more than the saline extinction group or the 0.75 mg/kg morphine treatment group. Moreover, the two higher dose morphine groups were suppressed as readily as the saline group that received no fear extinction. These results are attributed to the antiemotionality effects of morphine.

  15. Comparing the context specificity of extinction and latent inhibition.

    Science.gov (United States)

    Miller, Ralph R; Laborda, Mario A; Polack, Cody W; Miguez, Gonzalo

    2015-12-01

    Exposure to a cue alone either before (i.e., latent inhibition treatment) or after (i.e., extinction) the cue is paired with an unconditioned stimulus results in attenuated conditioned responding to the cue. Here we report two experiments in which potential parallels between the context specificity of the effects of extinction and latent inhibition treatments were directly compared in a lick suppression preparation with rats. The reversed ordering of conditioning and nonreinforcement in extinction and latent inhibition designs allowed us to examine the effect of training order on the context specificity of what is learned given phasic reinforcement and nonreinforcement of a target cue. Experiment 1 revealed that when conditioned-stimulus (CS) conditioning and CS nonreinforcement were administered in the same context, both extinction and latent inhibition treatments had reduced impacts on test performance, relative to excitatory conditioning when testing occurred outside the treatment context. Similarly, Experiment 2 showed that when conditioning was administered in one context and nonreinforcement was administered in a second context, the effects of both extinction and latent inhibition treatments were attenuated when testing occurred in a neutral context, relative to the context in which the CS was nonreinforced. The observed context specificity of extinction and latent inhibition treatments has been previously reported in both cases, but not in a single experiment under otherwise identical conditions. The results of the two experiments convergently suggest that memory of nonreinforcement becomes context dependent after a cue is both reinforced and nonreinforced, independent of the order of training.

  16. Issues in the extinction of specific stimulus-outcome associations in Pavlovian conditioning.

    Science.gov (United States)

    Delamater, Andrew R

    2012-05-01

    This paper reviews a variety of studies designed to examine the effects of extinction upon control by specific stimulus-outcome (S-O) associations in Pavlovian conditioning. Studies conducted with rats in a magazine approach conditioning paradigm have shown that control by specific S-O associations is normally unaffected by extinction treatments, although other aspects of conditioned responding seem affected in a more enduring way. However, recent work suggests that extinction can undermine control by such associations if it is administered after the conditioned stimulus is weakly encoded. The results from these studies suggest that it may be important to consider multiple response systems in assessing the impact of extinction. Studies conducted with the flavor preference learning paradigm in rats also show that specific S-O associations can be undermined by procedures that involve presenting a flavor cue in the absence of its associated nutrient. These findings provide no support for the view that flavor preference learning necessarily entails some unique learning process that differs from more conventional processes. As in other situations, some of these effects likely involve a masking process, but the extent to which masking or true associative weakening occurs in extinction more generally is a topic that is not well understood. Finally, we present some data to suggest that extinction also involves conditional "occasion-setting" control by contextual cues. Special procedures are recommended in assessing such learning when the goal is to distinguish this form of learning from other more conventional mechanisms of extinction.

  17. Mass Extinctions in Earth's History

    Science.gov (United States)

    Ward, P. D.

    2002-12-01

    Mass extinctions are short intervals of elevated species death. Possible causes of Earth's mass extinctions are both external (astronomical) and internal (tectonic and biotic changes from planetary mechanisms). Paleontologists have identified five "major" mass extinctions (>50 die-off in less than a million years) and more than 20 other minor events over the past 550 million years. Earlier major extinction events undoubtedly also occurred, but we have no fossil record; these were probably associated with, for example, the early heavy bombardment that cleared out the solar system, the advent of oxygen in the atmosphere, and various "snowball Earth" events. Mass extinctions are viewed as both destructive (species death ) and constructive, in that they allow evolutionary innovation in the wake of species disappearances. From an astrobiological perspective, mass extinctions must be considered as able both to reduce biodiversity and even potentially end life on any planet. Of the five major mass extinctions identified on Earth, only one (the Cretaceous/Tertiary event 65 million years ago that famously killed off the dinosaurs ) is unambiguously related to the impact of an asteroid or comet ( 10-km diameter). The Permian/Triassic (250 Myr ago) and Triassic/Jurassic (202 Myr ago) events are now the center of debate between those favoring impact and those suggesting large volume flooding by basaltic lavas. The final two events, Ordovician (440 Myr ago) and Devonian (370 Myr ago) have no accepted causal mechanisms.

  18. Extinction reveals that primary sensory cortex predicts reinforcement outcome

    OpenAIRE

    Bieszczad, Kasia M.; Weinberger, Norman M.

    2012-01-01

    Primary sensory cortices are traditionally regarded as stimulus analyzers. However, studies of associative learning-induced plasticity in the primary auditory cortex (A1) indicate involvement in learning, memory and other cognitive processes. For example, the area of representation of a tone becomes larger for stronger auditory memories and the magnitude of area gain is proportional to the degree that a tone becomes behaviorally important. Here, we used extinction to investigate whether “beha...

  19. Orbitofrontal cortex inactivation impairs between- but not within-session Pavlovian extinction: an associative analysis.

    Science.gov (United States)

    Panayi, Marios C; Killcross, Simon

    2014-02-01

    The orbitofrontal cortex (OFC) is argued to be the neural locus of Pavlovian outcome expectancies. Reinforcement learning theories argue that extinction learning in Pavlovian procedures is caused by the discrepancy between the expected value of the outcome (US) that is elicited by a predictive stimulus (CS), and the lack of experienced US. If the OFC represents Pavlovian outcome expectancies that are necessary for extinction learning, then disrupting OFC function prior to extinction training should impair extinction learning. This was tested. In experiment 1, Long Evans rats received infusions of saline or muscimol targeting the lateral OFC prior to three appetitive Pavlovian extinction sessions. Muscimol infused into the OFC disrupted between-session but not within-session extinction behaviour. This finding was not due to muscimol infusions disrupting the memory consolidation process per se as there was no effect of muscimol infusion when administered immediately post session (experiment 2). These findings support a role for the OFC in representing outcome expectancies that are necessary for learning. A number of ways in which disrupting outcome expectancy information might block learning will be discussed in the context of traditional associative learning theories and the associative structures they depend on.

  20. ACTH Prevents Deficits in Fear Extinction Associated with Early Life Seizures

    Directory of Open Access Journals (Sweden)

    Andrew T Massey

    2016-05-01

    Full Text Available Early life seizures are often associated with cognitive and psychiatric comorbidities that are detrimental to quality of life. In a rat model of early life seizures (ELS, we explored long-term cognitive outcomes in adult rats. Using ACTH, an endogeneous HPA-axis hormone given to children with severe epilepsy, we sought to prevent cognitive deficits. Through comparisons with dexamethasone, we sought to dissociate the corticosteroid effects of ACTH from other potential mechanisms of action. We found that while rats with a history of ELS were able to acquire a conditioned fear learning paradigm as well as controls, these rats had significant deficits in their ability to extinguish fearful memories. ACTH treatment did not alter any seizure parameters but nevertheless was able to significantly improve this fear extinction, while dexamethasone treatment during the same period did not. This ACTH effect was specific for fear extinction deficits and not for spatial learning deficits in a water maze. Additionally, ACTH did not alter seizure latency or duration suggesting that cognitive and seizure outcomes may be dissociable. Expression levels of melanocortin receptors, which bind ACTH, were found to be significantly lower in animals that had experienced ELS than in control animals, potentially implicating central melanocortin receptor dysregulation in the effects of ELS and suggesting a mechanism of action for ACTH. Taken together, these data suggest that early treatment with ACTH can have significant long-term consequences for cognition in animals with a history of ELS independently of seizure cessation, and may act in part through a CNS melanocortin receptor pathway.

  1. Extinction under a behavioral microscope: isolating the sources of decline in operant response rate.

    Science.gov (United States)

    Cheung, Timothy H C; Neisewander, Janet L; Sanabria, Federico

    2012-05-01

    Extinction performance is often used to assess underlying psychological processes without the interference of reinforcement. For example, in the extinction/reinstatement paradigm, motivation to seek drug is assessed by measuring responding elicited by drug-associated cues without drug reinforcement. However, extinction performance is governed by several psychological processes that involve motivation, memory, learning, and motoric functions. These processes are confounded when overall response rate is used to measure performance. Based on evidence that operant responding occurs in bouts, this paper proposes an analytic procedure that separates extinction performance into several behavioral components: (1-3) the baseline bout initiation rate, within-bout response rate, and bout length at the onset of extinction; (4-6) their rates of decay during extinction; (7) the time between extinction onset and the decline of responding; (8) the asymptotic response rate at the end of extinction; (9) the refractory period after each response. Data that illustrate the goodness of fit of this analytic model are presented. This paper also describes procedures to isolate behavioral components contributing to extinction performance and make inferences about experimental effects on these components. This microscopic behavioral analysis allows the mapping of different psychological processes to distinct behavioral components implicated in extinction performance, which may further our understanding of the psychological effects of neurobiological treatments.

  2. Low-frequency stimulation of the ventral hippocampus facilitates extinction of contextual fear.

    Science.gov (United States)

    Cleren, Carine; Tallarida, Isabelle; Guiniec, Emilie Le; Janin, François; Nachon, Ophélie; Canini, Frédéric; Spennato, Guillaume; Moreau, Jean-Luc; Garcia, René

    2013-03-01

    Difficulties to treat fear-associated disorders, including posttraumatic stress disorder, are thought to result from dysfunction in fear extinction learning and/or memory. Animal studies on extinction modulation are therefore promising for the development of new treatments. Recent rat studies, including ones using low-frequency stimulation (LFS), have demonstrated that the ventral hippocampus (VH) modulates extinction memory. The present study explores whether the VH also modulates extinction learning. For this, rats were implanted with stimulating electrodes in the VH and experienced contextual fear conditioning, followed 6 or 24 h later by VH LFS and three sessions of extinction training. We found that, whatever the delay used (6 or 24 h), animals that received VH LFS displayed persistent low levels of freezing from the second extinction session, whereas control rats showed low levels of freezing only during the third session. In animals submitted to a stress condition (provoked by a single inescapable foot-shock followed by three sessions of situational reminders) prior to fear conditioning, VH LFS also reduced freezing levels, which, in contrast, remained high in control rats during the course of extinction training. These data suggest that LFS, targeting the VH, may be useful in reducing fear responses during extinction learning.

  3. Mechanisms governing the reactivation-dependent destabilization of memories and their role in extinction

    OpenAIRE

    Charlotte Rachael Flavell; Elliot eLambert; Winters, Boyer D.; Bredy, Timothy W.

    2013-01-01

    The extinction of learned associations has traditionally been considered to involve new learning, which competes with the original memory for control over behaviour. However, a recent resurgence of interest in reactivation-dependent amnesia has revealed that the retrieval of fear-related memory (with what is essentially a brief extinction session) can result in it’s destabilization. This review discusses some of the cellular and molecular mechanisms that are involved in the destabilization of...

  4. Enhanced extinction of aversive memories by high-frequency stimulation of the rat infralimbic cortex.

    Directory of Open Access Journals (Sweden)

    Mouna Maroun

    Full Text Available Electrical stimulation of the rodent medial prefrontal cortex (mPFC, including the infralimbic cortex (IL, immediately prior to or during fear extinction training facilitates extinction memory. Here we examined the effects of high-frequency stimulation (HFS of the rat IL either prior to conditioning or following retrieval of the conditioned memory, on extinction of Pavlovian fear and conditioned taste aversion (CTA. IL-HFS applied immediately after fear memory retrieval, but not three hours after retrieval or prior to conditioning, subsequently reduced freezing during fear extinction. Similarly, IL-HFS given immediately, but not three hours after, retrieval of a CTA memory reduced aversion during extinction. These data indicate that HFS of the IL may be an effective method for reducing both learned fear and learned aversion.

  5. Failure of α-MSH to delay extinction of conditioned avoidance behavior in rats with lesions in the parafascicular nuclei of the thalamus

    NARCIS (Netherlands)

    Bohus, B.; Wied, D. de

    1967-01-01

    Bilateral lesions in the thalamic parafascicular area facilitate the rate of extinction of a conditioned avoidance response without affecting avoidance learning. Treatment with long-acting α-MSH during extinction failed to affect the rate of extinction of the avoidance response. Since this peptide d

  6. The Sixth Great Mass Extinction

    Science.gov (United States)

    Wagler, Ron

    2012-01-01

    Five past great mass extinctions have occurred during Earth's history. Humanity is currently in the midst of a sixth, human-induced great mass extinction of plant and animal life (e.g., Alroy 2008; Jackson 2008; Lewis 2006; McDaniel and Borton 2002; Rockstrom et al. 2009; Rohr et al. 2008; Steffen, Crutzen, and McNeill 2007; Thomas et al. 2004;…

  7. Extinction and the associative structure of heterogeneous instrumental chains.

    Science.gov (United States)

    Thrailkill, Eric A; Bouton, Mark E

    2016-09-01

    Drug abuse, overeating, and smoking are all examples of instrumental behaviors that often involve chains or sequences of behavior. A behavior chain is minimally composed of a procurement response that is required in order for a subsequent consumption response to be reinforced. Despite the translational importance of behavior chains, few studies have attempted to understand what binds them together and takes them apart. This article surveys the development of the heterogeneous instrumental chain method and introduces recent findings that have used extinction to analyze the associative content of (what is learned in) the chain. Chained responses that are occasion-set by their own discriminative stimuli may be directly associated; extinction of the procurement response weakens its associated consumption response, and extinction of the consumption response weakens its associated procurement response. Extinction itself involves learning to inhibit the response. Extinguished chained responses are subject to renewal when they are tested either back in the acquisition context or in a new context. In addition, a consumption response that is extinguished outside its chain is renewed when returned to the context of the preceding response in the chain. Research on heterogeneous behavior chains can provide important insights into an important but often overlooked aspect of instrumental learning.

  8. Extinction, relapse, and behavioral momentum.

    Science.gov (United States)

    Podlesnik, Christopher A; Shahan, Timothy A

    2010-05-01

    Previous experiments on behavioral momentum have shown that relative resistance to extinction of operant behavior in the presence of a discriminative stimulus depends upon the baseline rate or magnitude of reinforcement associated with that stimulus (i.e., the Pavlovian stimulus-reinforcer relation). Recently, we have shown that relapse of operant behavior in reinstatement, resurgence, and context renewal preparations also is a function of baseline stimulus-reinforcer relations. In this paper we present new data examining the role of baseline stimulus-reinforcer relations on resistance to extinction and relapse using a variety of baseline training conditions and relapse operations. Furthermore, we evaluate the adequacy of a behavioral momentum based model in accounting for the results. The model suggests that relapse occurs as a result of a decrease in the disruptive impact of extinction precipitated by a change in circumstances associated with extinction, and that the degree of relapse is a function of the pre-extinction baseline Pavlovian stimulus-reinforcer relation. Across experiments, relative resistance to extinction and relapse were greater in the presence of stimuli associated with more favorable conditions of reinforcement and were positively related to one another. In addition, the model did a good job in accounting for these effects. Thus, behavioral momentum theory may provide a useful quantitative approach for characterizing how differential reinforcement conditions contribute to relapse of operant behavior.

  9. Increases in Doublecortin Immunoreactivity in the Dentate Gyrus following Extinction of Heroin-Seeking Behavior

    Directory of Open Access Journals (Sweden)

    Megan P. Hicks

    2012-01-01

    Full Text Available Adult-generated neurons in the dentate gyrus (DG of the hippocampus play a role in various forms of learning and memory. However, adult born neurons in the DG, while still at an immature stage, exhibit unique electrophysiological properties and are also functionally implicated in learning and memory processes. We investigated the effects of extinction of drug-seeking behavior on the formation of immature neurons in the DG as assessed by quantification of doublecortin (DCX immunoreactivity. Rats were allowed to self-administer heroin (0.03 mg/kg/infusion for 12 days and then subjected either to 10 days of extinction training or forced abstinence. We also examined extinction responding patterns following heroin self-administration in glial fibrillary acidic protein thymidine kinase (GFAP-tk transgenic mice, which have been previously demonstrated to show reduced formation of immature and mature neurons in the DG following treatment with ganciclovir (GCV. We found that extinction training increased DCX immunoreactivity in the dorsal DG as compared with animals undergoing forced abstinence, and that GCV-treated GFAP-tk mice displayed impaired extinction learning as compared to saline-treated mice. Our results suggest that extinction of drug-seeking behavior increases the formation of immature neurons in the DG and that these neurons may play a functional role in extinction learning.

  10. Increases in doublecortin immunoreactivity in the dentate gyrus following extinction of heroin-seeking behavior.

    Science.gov (United States)

    Hicks, Megan P; Wischerath, Kelly C; Lacrosse, Amber L; Olive, M Foster

    2012-01-01

    Adult-generated neurons in the dentate gyrus (DG) of the hippocampus play a role in various forms of learning and memory. However, adult born neurons in the DG, while still at an immature stage, exhibit unique electrophysiological properties and are also functionally implicated in learning and memory processes. We investigated the effects of extinction of drug-seeking behavior on the formation of immature neurons in the DG as assessed by quantification of doublecortin (DCX) immunoreactivity. Rats were allowed to self-administer heroin (0.03 mg/kg/infusion) for 12 days and then subjected either to 10 days of extinction training or forced abstinence. We also examined extinction responding patterns following heroin self-administration in glial fibrillary acidic protein thymidine kinase (GFAP-tk) transgenic mice, which have been previously demonstrated to show reduced formation of immature and mature neurons in the DG following treatment with ganciclovir (GCV). We found that extinction training increased DCX immunoreactivity in the dorsal DG as compared with animals undergoing forced abstinence, and that GCV-treated GFAP-tk mice displayed impaired extinction learning as compared to saline-treated mice. Our results suggest that extinction of drug-seeking behavior increases the formation of immature neurons in the DG and that these neurons may play a functional role in extinction learning.

  11. Learning and memory alterations are associated with hippocampal N-acetylaspartate in a rat model of depression as measured by 1H-MRS.

    Directory of Open Access Journals (Sweden)

    Guangjun Xi

    Full Text Available It is generally accepted that cognitive processes, such as learning and memory, are affected in depression. The present study used a rat model of depression, chronic unpredictable mild stress (CUMS, to determine whether hippocampal volume and neurochemical changes were involved in learning and memory alterations. A further aim was to determine whether these effects could be ameliorated by escitalopram treatment, as assessed with the non-invasive techniques of structural magnetic resonance imaging (MRI and magnetic resonance spectroscopy (MRS. Our results demonstrated that CUMS had a dramatic influence on spatial cognitive performance in the Morris water maze task, and CUMS reduced the concentration of neuronal marker N-acetylaspartate (NAA in the hippocampus. These effects could be significantly reversed by repeated administration of escitalopram. However, neither chronic stress nor escitalopram treatment influenced hippocampal volume. Of note, the learning and memory alterations of the rats were associated with right hippocampal NAA concentration. Our results indicate that in depression, NAA may be a more sensitive measure of cognitive function than hippocampal volume.

  12. Task-specific enhancement of hippocampus-dependent learning in mice deficient in monoacylglycerol lipase, the major hydrolyzing enzyme of the endocannabinoid 2-arachidonoylglycerol

    Directory of Open Access Journals (Sweden)

    Yasushi eKishimoto

    2015-06-01

    Full Text Available Growing evidence indicates that the endocannabinoid system is important for the acquisition and/or extinction of learning and memory. However, it is unclear which endocannabinoid(s play(s a crucial role in these cognitive functions, especially memory extinction. To elucidate the physiological role of 2-arachidonoylglycerol (2-AG, a major endocannabinoid, in behavioral and cognitive functions, we conducted a comprehensive behavioral test battery in knockout (KO mice deficient in monoacylglycerol lipase (MGL, the major hydrolyzing enzyme of 2-AG. We found age-dependent increases in spontaneous physical activity in MGL KO mice. Next, we tested the MGL KO mice using 5 hippocampus-dependent learning paradigms (i.e., Morris water maze [MWM], contextual fear conditioning, novel object recognition test, trace eyeblink conditioning, and water-finding test. In the MWM, MGL KO mice showed normal acquisition of reference memory, but exhibited significantly faster extinction of the learned behavior. Moreover, they showed faster memory acquisition on the reversal-learning task of the MWM. In contrast, in the contextual fear conditioning, MGL KO mice tended to show slower memory extinction. In the novel object recognition and water-finding tests, MGL KO mice exhibited enhanced memory acquisition. Trace eyeblink conditioning was not altered in MGL KO mice throughout the acquisition and extinction phases. These results indicate that 2-AG signaling is important for hippocampus-dependent learning and memory, but its contribution is highly task-dependent.

  13. Do you know the extinction in your young massive cluster?

    CERN Document Server

    De Marchi, Guido; Sabbi, Elena

    2015-01-01

    Up to ages of ~100 Myr, massive clusters are still swamped in large amounts of gas and dust, with considerable and uneven levels of extinction. At the same time, large grains (ices?) produced by type II supernovae profoundly alter the interstellar medium (ISM), thus resulting in extinction properties very different from those of the diffuse ISM. To obtain physically meaningful parameters of stars, from basic luminosities and effective temperatures to masses and ages, we must understand and measure the local extinction law. This problem affects all the massive young clusters discussed in his volume. We have developed a powerful method to unambiguously determine the extinction law in an uniform way across a cluster field, using multi-band photometry of red giant stars belonging to the red clump (RC). In the Large Magellanic Cloud, with about 20 RC stars per arcmin^2, we can easily derive a solid and self-consistent absolute extinction curve over the entire wavelength range of the photometry. Here, we present th...

  14. Thermal Transgressions and Phanerozoic Extinctions

    Science.gov (United States)

    Worsley, T. R.; Kidder, D. L.

    2007-12-01

    A number of significant Phanerozoic extinctions are associated with marine transgressions that were probably driven by rapid ocean warming. The conditions associated with what we call thermal transgressions are extremely stressful to life on Earth. The Earth system setting associated with end-Permian extinction exemplifies an end-member case of our model. The conditions favoring extreme warmth and sea-level increases driven by thermal expansion are also conducive to changes in ocean circulation that foster widespread anoxia and sulfidic subsurface ocean waters. Equable climates are characterized by reduced wind shear and weak surface ocean circulation. Late Permian and Early Triassic thermohaline circulation differs considerably from today's world, with minimal polar sinking and intensified mid-latitude sinking that delivers sulfate from shallow evaporative areas to deeper water where it is reduced to sulfide. Reduced nutrient input to oceans from land at many of the extinction intervals results from diminished silicate weathering and weakened delivery of iron via eolian dust. The falloff in iron-bearing dust leads to minimal nitrate production, weakening food webs and rendering faunas and floras more susceptible to extinction when stressed. Factors such as heat, anoxia, ocean acidification, hypercapnia, and hydrogen sulfide poisoning would significantly affect these biotas. Intervals of tectonic quiescence set up preconditions favoring extinctions. Reductions in chemical silicate weathering lead to carbon dioxide buildup, oxygen drawdown, nutrient depletion, wind and ocean current abatement, long-term global warming, and ocean acidification. The effects of extinction triggers such as large igneous provinces, bolide impacts, and episodes of sudden methane release are more potent against the backdrop of our proposed preconditions. Extinctions that have characteristics we call for in the thermal transgressions include the Early Cambrian Sinsk event, as well as

  15. Extinction Laws toward Stellar Sources within a Dusty Circumstellar Medium and Implications for Type Ia Supernovae

    Science.gov (United States)

    Nagao, Takashi; Maeda, Keiichi; Nozawa, Takaya

    2016-06-01

    Many astronomical objects are surrounded by dusty environments. In such dusty objects, multiple scattering processes of photons by circumstellar (CS) dust grains can effectively alter extinction properties. In this paper, we systematically investigate the effects of multiple scattering on extinction laws for steady-emission sources surrounded by the dusty CS medium using a radiation transfer simulation based on the Monte Carlo technique. In particular, we focus on whether and how the extinction properties are affected by properties of CS dust grains by adopting various dust grain models. We confirm that behaviors of the (effective) extinction laws are highly dependent on the properties of CS grains, especially the total-to-selective extinction ratio R V , which characterizes the extinction law and can be either increased or decreased and compared with the case without multiple scattering. We find that the criterion for this behavior is given by a ratio of albedos in the B and V bands. We also find that either small silicate grains or polycyclic aromatic hydrocarbons are necessary for realizing a low value of R V as often measured toward SNe Ia if the multiple scattering by CS dust is responsible for their non-standard extinction laws. Using the derived relations between the properties of dust grains and the resulting effective extinction laws, we propose that the extinction laws toward dusty objects could be used to constrain the properties of dust grains in CS environments.

  16. Exogenous prenatal corticosterone exposure mimics the effects of prenatal stress on adult brain stress response systems and fear extinction behavior.

    Science.gov (United States)

    Bingham, Brian C; Sheela Rani, C S; Frazer, Alan; Strong, Randy; Morilak, David A

    2013-11-01

    Exposure to early-life stress is a risk factor for the development of cognitive and emotional disorders later in life. We previously demonstrated that prenatal stress (PNS) in rats results in long-term, stable changes in central stress-response systems and impairs the ability to extinguish conditioned fear responding, a component of post-traumatic stress disorder (PTSD). Maternal corticosterone (CORT), released during prenatal stress, is a possible mediator of these effects. The purpose of the present study was to investigate whether fetal exposure to CORT at levels induced by PNS is sufficient to alter the development of adult stress neurobiology and fear extinction behavior. Pregnant dams were subject to either PNS (60 min immobilization/day from ED 14-21) or a daily injection of CORT (10mg/kg), which approximated both fetal and maternal plasma CORT levels elicited during PNS. Control dams were given injections of oil vehicle. Male offspring were allowed to grow to adulthood undisturbed, at which point they were sacrificed and the medial prefrontal cortex (mPFC), hippocampus, hypothalamus, and a section of the rostral pons containing the locus coeruleus (LC) were dissected. PNS and prenatal CORT treatment decreased glucocorticoid receptor protein levels in the mPFC, hippocampus, and hypothalamus when compared to control offspring. Both treatments also decreased tyrosine hydroxylase levels in the LC. Finally, the effect of prenatal CORT exposure on fear extinction behavior was examined following chronic stress. Prenatal CORT impaired both acquisition and recall of cue-conditioned fear extinction. This effect was additive to the impairment induced by previous chronic stress. Thus, these data suggest that fetal exposure to high levels of maternal CORT is responsible for many of the lasting neurobiological consequences of PNS as they relate to the processes underlying extinction of learned fear. The data further suggest that adverse prenatal environments constitute a

  17. Reintroduction of locally extinct vertebrates impacts arid soil fungal communities.

    Science.gov (United States)

    Clarke, Laurence J; Weyrich, Laura S; Cooper, Alan

    2015-06-01

    Introduced species have contributed to extinction of native vertebrates in many parts of the world. Changes to vertebrate assemblages are also likely to alter microbial communities through coextinction of some taxa and the introduction of others. Many attempts to restore degraded habitats involve removal of exotic vertebrates (livestock and feral animals) and reintroduction of locally extinct species, but the impact of such reintroductions on microbial communities is largely unknown. We used high-throughput DNA sequencing of the fungal internal transcribed spacer I (ITS1) region to examine whether replacing exotic vertebrates with reintroduced native vertebrates led to changes in soil fungal communities at a reserve in arid central Australia. Soil fungal diversity was significantly different between dune and swale (interdune) habitats. Fungal communities also differed significantly between sites with exotic or reintroduced native vertebrates after controlling for the effect of habitat. Several fungal operational taxonomic units (OTUs) found exclusively inside the reserve were present in scats from reintroduced native vertebrates, providing a direct link between the vertebrate assemblage and soil microbial communities. Our results show that changes to vertebrate assemblages through local extinctions and the invasion of exotic species can alter soil fungal communities. If local extinction of one or several species results in the coextinction of microbial taxa, the full complement of ecological interactions may never be restored.

  18. Mechanisms governing the reactivation-dependent destabilization of memories and their role in extinction

    Directory of Open Access Journals (Sweden)

    Charlotte Rachael Flavell

    2013-12-01

    Full Text Available The extinction of learned associations has traditionally been considered to involve new learning, which competes with the original memory for control over behaviour. However, a recent resurgence of interest in reactivation-dependent amnesia has revealed that the retrieval of fear-related memory (with what is essentially a brief extinction session can result in it’s destabilization. This review discusses some of the cellular and molecular mechanisms that are involved in the destabilization of a memory following it’s reactivation and/or extinction, and investigates the evidence that extinction may involve both new learning as well as a partial destabilization-induced erasure of the original memory trace.

  19. Effects of endocannabinoid and endovanilloid systems on aversive memory extinction.

    Science.gov (United States)

    Laricchiuta, Daniela; Centonze, Diego; Petrosini, Laura

    2013-11-01

    In contextual fear conditioning animals have to integrate various elemental stimuli into a coherent representation of the condition and then associate context representation with punishment. Although several studies indicated the modulating role of endocannabinoid system (ECS) on the associative learning, ECS effect on contextual fear conditioning requires further investigations. The present study assessed the effects of the increased endocannabinoid anandamide (AEA) tone on acquisition, retrieval and extinction of the contextual fear conditioning. Given that AEA may bind to cannabinoid type 1 (CB1) receptors as well as to postsynaptic ionotropic Transient Receptor Potential Vanilloid type 1 (TRPV1) channels, particular attention was paid in determining how the increased AEA tone influenced fear responses. Furthermore, it was investigated how the ECS modulated the effects of stress-sensitization on fear response. Thus, mice submitted or not to a social defeat stress protocol were treated with drugs acting on ECS, CB1 receptors or TRPV1 channels and tested in a contextual fear conditioning whose conditioning, retrieval and extinction phases were analyzed. ECS activation influenced the extinction process and contrasted the stress effects on fear memory. Furthermore, CB1 receptor antagonist blocked and TRPV1 channel antagonist promoted short- and long-term extinction. The present study indicates that ECS controls the extinction of aversive memories in the contextual fear conditioning.

  20. How partial reinforcement of food cues affects the extinction and reacquisition of appetitive responses. A new model for dieting success?

    Science.gov (United States)

    van den Akker, Karolien; Havermans, Remco C; Bouton, Mark E; Jansen, Anita

    2014-10-01

    Animals and humans can easily learn to associate an initially neutral cue with food intake through classical conditioning, but extinction of learned appetitive responses can be more difficult. Intermittent or partial reinforcement of food cues causes especially persistent behaviour in animals: after exposure to such learning schedules, the decline in responding that occurs during extinction is slow. After extinction, increases in responding with renewed reinforcement of food cues (reacquisition) might be less rapid after acquisition with partial reinforcement. In humans, it may be that the eating behaviour of some individuals resembles partial reinforcement schedules to a greater extent, possibly affecting dieting success by interacting with extinction and reacquisition. Furthermore, impulsivity has been associated with less successful dieting, and this association might be explained by impulsivity affecting the learning and extinction of appetitive responses. In the present two studies, the effects of different reinforcement schedules and impulsivity on the acquisition, extinction, and reacquisition of appetitive responses were investigated in a conditioning paradigm involving food rewards in healthy humans. Overall, the results indicate both partial reinforcement schedules and, possibly, impulsivity to be associated with worse extinction performance. A new model of dieting success is proposed: learning histories and, perhaps, certain personality traits (impulsivity) can interfere with the extinction and reacquisition of appetitive responses to food cues and they may be causally related to unsuccessful dieting.

  1. Differential participation of temporal structures in the consolidation and reconsolidation of taste aversion extinction.

    Science.gov (United States)

    Garcia-Delatorre, Paola; Rodríguez-Ortiz, Carlos J; Balderas, Israela; Bermúdez-Rattoni, Federico

    2010-09-01

    The extinction process has been described as the decline in the frequency or intensity of the conditioned response following the withdrawal of reinforcement. Hence, experimental extinction does not reflect loss of the original memory, but rather reflects new learning, which in turn requires consolidation in order to be maintained in the long term. During extinction of conditioned taste aversion (CTA), a taste previously associated with aversive consequences acquires a safe status through continuous presentations of the flavor with no aversive consequence. In addition, reconsolidation has been defined as the labile state of a consolidated memory after its reactivation by the presentation of relevant information. In this study, we analyzed structures from the temporal lobe that could be involved in consolidation and reconsolidation of extinction of CTA by means of new protein synthesis. Our results showed that protein synthesis in the hippocampus (HC), the perirhinal cortex (PR) and the insular cortex (IC) of rats participate in extinction consolidation, whereas the basolateral amygdala plays no part in this phenomenon. Furthermore, we found that inhibition of protein synthesis in the IC in a third extinction trial had an effect on reconsolidation of extinction. The participation of the HC in taste memory has been described as a downmodulator for CTA consolidation, and has been related to a context-taste association. Altogether, these data suggest that extinction of aversive taste memories are subserved by the IC, HC and PR, and that extinction can undergo reconsolidation, a process depending only on the IC.

  2. Neural changes in extinction recall following prolonged exposure treatment for PTSD: A longitudinal fMRI study

    Directory of Open Access Journals (Sweden)

    Liat Helpman, PhD

    2016-01-01

    Conclusions: Prolonged exposure treatment appears to alter neural activation in PTSD patients during recall of fear extinction, and change in extinction recall (measured by SCR is associated with symptom reduction. We discuss results in the context of neural systems involved in response to affective stimuli.

  3. The extinction of the dinosaurs.

    Science.gov (United States)

    Brusatte, Stephen L; Butler, Richard J; Barrett, Paul M; Carrano, Matthew T; Evans, David C; Lloyd, Graeme T; Mannion, Philip D; Norell, Mark A; Peppe, Daniel J; Upchurch, Paul; Williamson, Thomas E

    2015-05-01

    Non-avian dinosaurs went extinct 66 million years ago, geologically coincident with the impact of a large bolide (comet or asteroid) during an interval of massive volcanic eruptions and changes in temperature and sea level. There has long been fervent debate about how these events affected dinosaurs. We review a wealth of new data accumulated over the past two decades, provide updated and novel analyses of long-term dinosaur diversity trends during the latest Cretaceous, and discuss an emerging consensus on the extinction's tempo and causes. Little support exists for a global, long-term decline across non-avian dinosaur diversity prior to their extinction at the end of the Cretaceous. However, restructuring of latest Cretaceous dinosaur faunas in North America led to reduced diversity of large-bodied herbivores, perhaps making communities more susceptible to cascading extinctions. The abruptness of the dinosaur extinction suggests a key role for the bolide impact, although the coarseness of the fossil record makes testing the effects of Deccan volcanism difficult.

  4. Measuring Galactic Extinction A Test

    CERN Document Server

    Arce, H G; Arce, Hector G.; Goodman, Alyssa A.

    1999-01-01

    We test the recently published all-sky reddening map of Schlegel, Finkbeiner & Davis (1998 [SFD]) using the extinction study of a region in the Taurus dark cloud complex by Arce & Goodman (1999 [AG]). In their study, AG use four different techniques to measure the amount and structure of the extinction toward Taurus, and all four techniques agree very well. Thus we believe that the AG results are a truthful representation of the extinction in the region and can be used to test the reliability of the SFD reddening map. The results of our test show that the SFD all-sky reddening map, which is based on data from COBE/DIRBE and IRAS/ISSA, overestimates the reddening by a factor of 1.3 to 1.5 in regions of smooth extinction with A_V > 0.5 mag. In some regions of steep extinction gradients the SFD map underestimates the reddening value, probably due to its low spatial resolution. We expect that the astronomical community will be using the SFD reddening map extensively. We offer this Letter as a cautionary n...

  5. FAAH inhibitor, URB-597, promotes extinction and CB(1) antagonist, SR141716, inhibits extinction of conditioned aversion produced by naloxone-precipitated morphine withdrawal, but not extinction of conditioned preference produced by morphine in rats.

    Science.gov (United States)

    Manwell, Laurie A; Satvat, Elham; Lang, Stefan T; Allen, Craig P; Leri, Francesco; Parker, Linda A

    2009-11-01

    Converging evidence suggests that the endogenous cannabinoid (eCB) system is involved in extinction of learned behaviours. Using operant and classical conditioning procedures, the potential of the fatty acid amide (FAAH) inhibitor, URB-597, and the CB(1) antagonist/inverse agonist, SR141716, to promote and inhibit (respectively) extinction of learned responses previously motivated by either rewarding or aversive stimuli was investigated. In the operant conditioning procedure (Expt. 1), rats previously trained to lever press for sucrose reward were administered URB-597 (0.3 mg/kg) or the CB(1) antagonist/inverse agonist SR141716 (2.5 mg/kg) prior to each of three extinction trials. In the conditioned floor preference procedure (Expts 2a-d), rats trained to associate morphine with one of two distinctive floors were administered one of several doses of the CB(1) antagonist/inverse agonist, AM-251 (Expt 2a) or URB-597 (Expt 2b and 2d) prior to each extinction/test trial wherein a choice of both floors was presented and prior to forced exposure to each floor (Expt 2c). In the conditioned floor aversion procedure (Expt. 3), rats trained to associate a naloxone-precipitated morphine withdrawal with a floor cue were administered URB-597 or SR141716 prior to each of 24 extinction/testing trials. URB-597 did not promote and SR141716 did not reduce extinction rates for sucrose reward-induced operant responding (Expt. 1) or morphine-induced conditioned floor preference (Expts. 2a-d). In contrast, URB-597 facilitated, whereas SR141716 impaired, extinction of the conditioned floor aversion (Expt. 3). These data support previous reports that the eCB system selectively facilitates extinction of aversive memories. URB-597 may prove useful in targeting extinction of aversively motivated behaviours.

  6. Auditory Cortex is Important in the Extinction of Two Different Tone-Based Conditioned Fear Memories in Rats

    OpenAIRE

    Eun Young Song; Boatman, Jeffrey A; Jung, Min W.; Kim, Jeansok J.

    2010-01-01

    Extensive fear extinction research is guided by the view that there are structures in the brain that develop inhibitory control over the expression of conditioned fear memories. While the medial prefrontal cortex has recently captured attention as the locus of plasticity essential for extinction of conditioned fear, the auditory cortex is another plausible cortical area involved in extinction learning since it is considered a sufficient conditioned stimulus (CS) pathway in tone fear conditio...

  7. Altered statistical learning and decision-making in methamphetamine dependence: Evidence from a two-armed bandit task

    Directory of Open Access Journals (Sweden)

    Katia M Harlé

    2015-12-01

    Full Text Available Understanding how humans weigh long-term and short-term goals is important for both basic cognitive science and clinical neuroscience, as substance users need to balance the appeal of an immediate high versus the long-term goal of sobriety. We use a computational model to identify learning and decision-making abnormalities in methamphetamine-dependent individuals (MDI, n=16 versus healthy control subjects (HCS, n=16, in a two-armed bandit task.In this task, subjects repeatedly choose between two arms with fixed but unknown reward rates. Each choice not only yields potential immediate reward but also information useful for long-term reward accumulation, thus pitting exploration against exploitation. We formalize the task as comprising a learning component, the updating of estimated reward rates based on ongoing observations, and a decision-making component, the choice among options based on current beliefs and uncertainties about reward rates. We model the learning component as iterative Bayesian inference (the Dynamic Belief Model, and the decision component using five competing decision policies: Win-stay/Lose-shift (WSLS, ε-Greedy, τ-Switch, Softmax, Knowledge Gradient. HCS and MDI significantly differ in how they learn about reward rates and use them to make decisions. HCS learn from past observations but weigh recent data more, and their decision policy is best fit as Softmax. MDI are more likely to follow the simple learning-independent policy of WSLS, and among MDI best fit by Softmax, they have more pessimistic prior beliefs about reward rates and are less likely to choose the option estimated to be most rewarding. Neurally, MDI’s tendency to avoid the most rewarding option is associated with a lower grey matter volume of the thalamic dorsal lateral nucleus. More broadly, our work illustrates the ability of our computational framework to help reveal subtle learning and decision-making abnormalities in substance use.

  8. Disturbance-mediated colonization-extinction dynamics in experimental protist metacommunities.

    Science.gov (United States)

    Fukumori, Kayoko; Livingston, George; Leibold, Mathew A

    2015-12-01

    Colonization-extinction dynamics and species sorting among habitats deter- mine the distribution of species within metacommunities. Theory suggests that disturbances reduce the importance of species sorting and enhance spatial patterning and stochastic effects, however this has not yet been experimentally shown. We examined how extinctions in a heterogeneous landscape of patches affects the influence of environmental, spatial, and stochastic factors on community composition in a simple two-species, two-habitat, protist metacommunity where each species dominates in a different habitat type. We imposed four different levels of random extinctions on local patches and monitored changes in the metacommunity through time. We found that near-steady state patterns of community variability developed relatively rapidly (within nine colonization-extinction cycles) and that increased extinction rate produced altered patterns of community regulation by reducing environmental control and increasing spatial and stochastic effects. Our results indicate a possible explanation for the combination of environmental, spatial and stochastic effects observed in natural metacommunities.

  9. Dimethoate accelerates the extinction of eyeblink conditioning in mice.

    Science.gov (United States)

    Valenzuela-Harrington, Mauricio; Castillo, Irene; Díaz, Corín; Alés, Inés; Rodríguez-Moreno, Antonio

    2012-01-01

    In agriculture, organophosphates are frequently used as insecticides and pesticides. These compounds decrease acetylcholine esterase (AChE) activity, thereby provoking an accumulation of the neurotransmitter acetylcholine at synapses and resulting in the over-stimulation of acetylcholine receptors. Using trace paradigms, we investigated the effects of dimethoate, a widely used organophosphate insecticide, on the classical conditioning of eyelid responses, a hippocampal-dependent mouse model of associative learning. Mice were conditioned with a trace shock-SHOCK paradigm having first implanted stimulating electrodes in the supraorbitary nerve and recording electrodes in the ipsilateral orbicularis oculi muscle. When these mice were injected with dimethoate (5, 20, 50mg/kg/day) they were capable of acquiring associative learning, and the latency and amplitude of their unconditioned eyelid responses were unaffected by the administration of the pesticide. However, dimethoate administration led to the rapid extinction of conditioned responses, suggesting that this organophosphate accelerates the extinction of this form of associative learning. Analysis of the motor function of these mice using the rotarod performance test revealed that motor function and performance clearly deteriorated following dimethoate administration, with no improvements over the following 4 days. Together these findings indicate that dimethoate accelerates the extinction of acquired conditioned responses, affecting associative learning and memory, and it impairs motor function and performance in mice.

  10. Mass extinctions and supernova explosions

    CERN Document Server

    Korschinek, Gunther

    2016-01-01

    A nearby supernova (SN) explosion could have negatively influenced life on Earth, maybe even been responsible for mass extinctions. Mass extinction poses a significant extinction of numerous species on Earth, as recorded in the paleontologic, paleoclimatic, and geological record of our planet. Depending on the distance between the Sun and the SN, different types of threats have to be considered, such as ozone depletion on Earth, causing increased exposure to the Sun's ultraviolet radiation, or the direct exposure of lethal x-rays. Another indirect effect is cloud formation, induced by cosmic rays in the atmosphere which result in a drop in the Earth's temperature, causing major glaciations of the Earth. The discovery of highly intensive gamma ray bursts (GRBs), which could be connected to SNe, initiated further discussions on possible life-threatening events in Earth's history. The probability that GRBs hit the Earth is very low. Nevertheless, a past interaction of Earth with GRBs and/or SNe cannot be exclude...

  11. Infectious Disease, Endangerment, and Extinction

    Directory of Open Access Journals (Sweden)

    Ross D. E. MacPhee

    2013-01-01

    Full Text Available Infectious disease, especially virulent infectious disease, is commonly regarded as a cause of fluctuation or decline in biological populations. However, it is not generally considered as a primary factor in causing the actual endangerment or extinction of species. We review here the known historical examples in which disease has, or has been assumed to have had, a major deleterious impact on animal species, including extinction, and highlight some recent cases in which disease is the chief suspect in causing the outright endangerment of particular species. We conclude that the role of disease in historical extinctions at the population or species level may have been underestimated. Recent methodological breakthroughs may lead to a better understanding of the past and present roles of infectious disease in influencing population fitness and other parameters.

  12. Potential Association of Lead Exposure During Early Development of Mice With Alteration of Hippocampus Nitric Oxide Levels and Learning Memory

    Institute of Scientific and Technical Information of China (English)

    LI SUN; ZHENG-YAN ZHAO; JIAN HU; XIE-LAI ZHOU

    2005-01-01

    Objective Chronic lead (Pb) exposure during development is known to produce learning deficits. Nitric oxide participates in the synaptic mechanisms involved in certain forms of learning and memory. This study was designed to clarify whether Pb-induced impairment in learning and memory was associated with the changes of nitric oxide levels in mice brains.Methods Sixty Balb/c mice aged 10 days were chosen. A model of lead exposure was established by drinking 0.025%, 0.05%,0.075% lead acetate, respectively for 8 weeks. The controls were orally given distilled water. The ability to learn and memorize was examined by open field test, T-water maze test. In parallel with the behavioral data, NO level of hippocampus tissue was detected by biochemical assay. Results Compared with control groups, (1) the weight of 0.075% group was significantly reduced (P<0.05); (2) The number of times in mice attaining the required standards in T-water maze test was lower in 0.075%group (P<0.01). No significant difference was found between experimental and control groups in open field test (P>0.05); (3)NO level of mouse hippocampus tissue was decreased in 0.075% group (P<0.01). Conclusions The findings suggest that decreased hippocampus NO level may contribute to the Pb-induced deficits in learning and memory processes.

  13. Habituation, latent inhibition, and extinction.

    Science.gov (United States)

    Jordan, Wesley P; Todd, Travis P; Bucci, David J; Leaton, Robert N

    2015-06-01

    In two conditioned suppression experiments with a latent inhibition (LI) design, we measured the habituation of rats in preexposure, their LI during conditioning, and then extinction over days. In the first experiment, lick suppression, the preexposed group (PE) showed a significant initial unconditioned response (UR) to the target stimulus and significant long-term habituation (LTH) of that response over days. The significant difference between the PE and nonpreexposed (NPE) groups on the first conditioning trial was due solely to the difference in their URs to the conditioned stimulus (CS)-a habituated response (PE) and an unhabituated response (NPE). In the second experiment, bar-press suppression, little UR to the target stimulus was apparent during preexposure, and no detectable LTH. Thus, there was no difference between the PE and NPE groups on the first conditioning trial. Whether the UR to the CS confounds the interpretation of LI (Exp. 1) or not (Exp. 2) can only be known if the UR is measured. In both experiments, LI was observed in acquisition. Also in both experiments, rats that were preexposed and then conditioned to asymptote were significantly more resistant to extinction than were the rats not preexposed. This result contrasts with the consistently reported finding that preexposure either produces less resistance to extinction or has no effect on extinction. The effect of stimulus preexposure survived conditioning to asymptote and was reflected directly in extinction. These two experiments provide a cautionary procedural note for LI experiments and have shown an unexpected extinction effect that may provide new insights into the interpretation of LI.

  14. Extinction risk of soil biota.

    Science.gov (United States)

    Veresoglou, Stavros D; Halley, John M; Rillig, Matthias C

    2015-11-23

    No species lives on earth forever. Knowing when and why species go extinct is crucial for a complete understanding of the consequences of anthropogenic activity, and its impact on ecosystem functioning. Even though soil biota play a key role in maintaining the functioning of ecosystems, the vast majority of existing studies focus on aboveground organisms. Many questions about the fate of belowground organisms remain open, so the combined effort of theorists and applied ecologists is needed in the ongoing development of soil extinction ecology.

  15. Interstellar Grains: Effect of Inclusions on Extinction

    CERN Document Server

    Katyal, Nisha; Vaidya, D B

    2011-01-01

    A composite dust grain model which simultaneously explains the observed interstellar extinction, polarization, IR emission and the abundance constraints, is required. We present a composite grain model, which is made up of a host silicate oblate spheroid and graphite inclusions. The interstellar extinction curve is evaluated in the spectral region 3.4-0.1$\\mu m$ using the extinction efficiencies of the composite spheroidal grains for three axial ratios. Extinction curves are computed using the discrete dipole approximation (DDA). The model curves are subsequently compared with the average observed interstellar extinction curve and with an extinction curve derived from the IUE catalogue data.

  16. Interstellar grains: Effect of inclusions on extinction

    Science.gov (United States)

    Katyal, N.; Gupta, R.; Vaidya, D. B.

    2011-10-01

    A composite dust grain model which simultaneously explains the observed interstellar extinction, polarization, IR emission and the abundance constraints, is required. We present a composite grain model, which is made up of a host silicate oblate spheroid and graphite inclusions. The interstellar extinction curve is evaluated in the spectral region 3.4-0.1 μm using the extinction efficiencies of composite spheroidal grains for three axial ratios. Extinction curves are computed using the discrete dipole approximation (DDA). The model curves are subsequently compared with the average observed interstellar extinction curve and with an extinction curve derived from the IUE catalogue data.

  17. Bidirectional synaptic plasticity in intercalated amygdala neurons and the extinction of conditioned fear responses.

    Science.gov (United States)

    Royer, S; Paré, D

    2002-01-01

    Classical fear conditioning is believed to result from potentiation of conditioned synaptic inputs in the basolateral amygdala. That is, the conditioned stimulus would excite more neurons in the central nucleus and, via their projections to the brainstem and hypothalamus, evoke fear responses. However, much data suggests that extinction of fear responses does not depend on the reversal of these changes but on a parallel NMDA-dependent learning that competes with the first one. Because they control impulse traffic from the basolateral amygdala to the central nucleus, GABAergic neurons of the intercalated cell masses are ideally located to implement this second learning. Consistent with this hypothesis, the present study shows that low- and high-frequency stimulation of basolateral afferents respectively induce long-term depression (LTD) and potentiation (LTP) of responses in intercalated cells. Moreover, induction of LTP and LTD is prevented by application of an NMDA antagonist. To determine how these activity-dependent changes are expressed, we tested whether LTD and LTP induction are associated with modifications in paired-pulse facilitation, an index of transmitter release probability. Only LTP induction was associated with a change in paired-pulse facilitation. Depotentiation of previously potentiated synapses did not revert the modification in paired pulse facilitation, suggesting that LTP is associated with presynaptic alterations, but that LTD and depotentiation depend on postsynaptic changes. Taken together, our results suggest that basolateral synapses onto intercalated neurons can express NMDA-dependent LTP and LTD, consistent with the possibility that intercalated neurons are a critical locus of plasticity for the extinction of conditioned fear responses. Ultimately, these plastic events may prevent conditioned amygdala responses from exciting neurons of the central nucleus, and thus from evoking conditioned fear responses.

  18. Endangered and Extinct Radioactivity

    Science.gov (United States)

    Leising, M. D.

    1993-07-01

    Gamma ray spectroscopy holds great promise for probing nucleosynthesis in individual nucleosynthesis events, via observations of short-lived radioactivity, and for measuring global galactic nucleosynthesis today with detections of longer-lived radioactivity. Many of the astrophysical issues addressed by these observations are precisely those that must be understood in order to interpret observations of extinct radioactivity in meteorites. It was somewhat surprising that the former case was realized first for a Type II supernova, when both 56Co [1] and 57Co [2] were detected in SN 1987A. These provide unprecedented constraints on models of Type II explosions. Live 26Al in the galaxy might come from Type II supernovae and their progenitors, and if this is eventually shown to be the case, can constrain massive star evolution, supernova nucleosynthesis, the galactic Type II supernova rate, and even models of the chemical evolution of the galaxy [3]. Titanium-44 is produced primarily in the alpha-rich freezeout from nuclear statistical equilibrium, possibly in Type Ia [4] and almost certainly in Type II supernovae [5]. The galactic recurrence time of these events is comparable to the 44Ti lifetime, so we expect to be able to see at most a few otherwise unseen 44Ti remnants at any given time. No such remnants have been detected yet [6]. Very simple arguments lead to the expectation that about 4 x 10^-4 M(sub)solar mass of 44Ca are produced per century. The product of the supernova frequency times the 44Ti yield per event must equal this number. Even assuming that only the latest event would be seen, rates in excess of 2 century^-1 are ruled out at >=99% confidence by the gamma ray limits. Only rates less than 0.3 century^-1 are acceptable at >5% confidence, and this means that the yield per event must be >10^-3 M(sub)solar mass to produce the requisite 44Ca. Rates this low are incompatible with current estimates for Type II supernovae and yields this high are also very

  19. Neuro-Linguistic Programming and Altered States: Encouraging Preparation for Learning in the Classroom for Students with Special Educational Needs

    Science.gov (United States)

    Kudliskis, Voldis

    2013-01-01

    In seeking to identify the processes associated with the immediate engagement of learning for students with mild special educational needs, this study examined the responses of an extraction group (n = 7) of 11- to 13-year-old students who participated in a number of lessons in which the opening episode involved the use of visualisation techniques…

  20. Continuous theta-burst stimulation (cTBS) over the lateral prefrontal cortex alters reinforcement learning bias

    NARCIS (Netherlands)

    Ott, D.V.M.; Ullsperger, M.; Jocham, G.; Neumann, J.; Klein, T.A.

    2011-01-01

    The prefrontal cortex is known to play a key role in higher-order cognitive functions. Recently, we showed that this brain region is active in reinforcement learning, during which subjects constantly have to integrate trial outcomes in order to optimize performance. To further elucidate the role of

  1. Continuous theta-burst stimulation (cTBS) over the lateral prefrontal cortex alters reinforcement learning bias.

    Science.gov (United States)

    Ott, Derek V M; Ullsperger, Markus; Jocham, Gerhard; Neumann, Jane; Klein, Tilmann A

    2011-07-15

    The prefrontal cortex is known to play a key role in higher-order cognitive functions. Recently, we showed that this brain region is active in reinforcement learning, during which subjects constantly have to integrate trial outcomes in order to optimize performance. To further elucidate the role of the dorsolateral prefrontal cortex (DLPFC) in reinforcement learning, we applied continuous theta-burst stimulation (cTBS) either to the left or right DLPFC, or to the vertex as a control region, respectively, prior to the performance of a probabilistic learning task in an fMRI environment. While there was no influence of cTBS on learning performance per se, we observed a stimulation-dependent modulation of reward vs. punishment sensitivity: Left-hemispherical DLPFC stimulation led to a more reward-guided performance, while right-hemispherical cTBS induced a more avoidance-guided behavior. FMRI results showed enhanced prediction error coding in the ventral striatum in subjects stimulated over the left as compared to the right DLPFC. Both behavioral and imaging results are in line with recent findings that left, but not right-hemispherical stimulation can trigger a release of dopamine in the ventral striatum, which has been suggested to increase the relative impact of rewards rather than punishment on behavior.

  2. D-Cycloserine Does Not Facilitate Fear Extinction by Reducing Conditioned Stimulus Processing or Promoting Conditioned Inhibition to Contextual Cues

    Science.gov (United States)

    Baker, Kathryn D.; McNally, Gavan P.; Richardson, Rick

    2012-01-01

    The NMDA receptor partial agonist d-cycloserine (DCS) enhances the extinction of learned fear in rats and exposure therapy in humans with anxiety disorders. Despite these benefits, little is known about the mechanisms by which DCS promotes the loss of fear. The present study examined whether DCS augments extinction retention (1) through reductions…

  3. Deletion of selenoprotein P results in impaired function of parvalbumin interneurons and alterations in fear learning and sensorimotor gating.

    Science.gov (United States)

    Pitts, M W; Raman, A V; Hashimoto, A C; Todorovic, C; Nichols, R A; Berry, M J

    2012-04-19

    One of the primary lines of defense against oxidative stress is the selenoprotein family, a class of proteins that contain selenium in the form of the 21st amino acid, selenocysteine. Within this class of proteins, selenoprotein P (Sepp1) is unique, as it contains multiple selenocysteine residues and is postulated to act in selenium transport. Recent findings have demonstrated that neuronal selenoprotein synthesis is required for the development of parvalbumin (PV)-interneurons, a class of GABAergic neurons involved in the synchronization of neural activity. To investigate the potential influence of Sepp1 on PV-interneurons, we first mapped the distribution of the Sepp1 receptor, ApoER2, and parvalbumin in the mouse brain. Our results indicate that ApoER2 is highly expressed on PV-interneurons in multiple brain regions. Next, to determine whether PV-interneuron populations are affected by Sepp1 deletion, we performed stereology on several brain regions in which we observed ApoER2 expression on PV-interneurons, comparing wild-type and Sepp1(-/-) mice. We observed reduced numbers of PV-interneurons in the inferior colliculus of Sepp1(-/-) mice, which corresponded with a regional increase in oxidative stress. Finally, as impaired PV-interneuron function has been implicated in several neuropsychiatric conditions, we performed multiple behavioral tests on Sepp1(-/-) mice. Our behavioral results indicate that Sepp1(-/-) mice have impairments in contextual fear extinction, latent inhibition, and sensorimotor gating. In sum, these findings demonstrate the important supporting role of Sepp1 on ApoER2-expressing PV-interneurons.

  4. A theoretical quantitative genetic study of negative ecological interactions and extinction times in changing environments

    Directory of Open Access Journals (Sweden)

    Jones Adam G

    2008-04-01

    Full Text Available Abstract Background Rapid human-induced changes in the environment at local, regional and global scales appear to be contributing to population declines and extinctions, resulting in an unprecedented biodiversity crisis. Although in the short term populations can respond ecologically to environmental alterations, in the face of persistent change populations must evolve or become extinct. Existing models of evolution and extinction in changing environments focus only on single species, even though the dynamics of extinction almost certainly depend upon the nature of species interactions. Results Here, I use a model of quantitative trait evolution in a two-species community to show that negative ecological interactions, such as predation and competition, can produce unexpected results regarding time to extinction. Under some circumstances, negative interactions can be expected to hasten the extinction of species declining in numbers. However, under other circumstances, negative interactions can actually increase times to extinction. This effect occurs across a wide range of parameter values and can be substantial, in some cases allowing a population to persist for 40 percent longer than it would in the absence of the species interaction. Conclusion This theoretical study indicates that negative species interactions can have unexpected positive effects on times to extinction. Consequently, detailed studies of selection and demographics will be necessary to predict the consequences of species interactions in changing environments for any particular ecological community.

  5. Timing of SCH 23390 administration influences extinction of conditioned hyperactivity in mice.

    Science.gov (United States)

    Rauhut, Anthony S

    2016-02-01

    The precise role of the dopamine subtype-1 (D1) receptor in differentially mediating extinction-related processes (memory retrieval vs. memory reconsolidation) in the conditioned hyperactivity paradigm is unknown. Thus, the present experiments determined the effect of a selective D1 receptor antagonist, SCH 23390, on extinction of conditioned hyperactivity when SCH 23390 was administered immediately after (memory reconsolidation; experiment 1) or before (memory retrieval; experiment 2) extinction sessions. Male, Swiss-Webster mice received subcutaneous injections of methamphetamine (1.0 mg/kg) associated with locomotor activity chambers (paired) or in their home cages (unpaired) during the acquisition phase. Following acquisition, paired and unpaired mice received an intraperitoneal injection of either vehicle (physiological saline) or SCH 23390 (0.0125, 0.025, 0.05 mg/kg) immediately after (experiment 1) or received vehicle or SCH 23390 (0.05 mg/kg) 30 min before (experiment 2), daily extinction sessions. Methamphetamine produced robust conditioned hyperactivity, followed by extinction. Furthermore, SCH 23390 (0.05 mg/kg) blocked expression of conditioned hyperactivity, without nonspecifically impairing locomotor activity, when administered before the extinction session, but did not alter the rate of extinction when administered immediately following the sessions. Taken together, these results suggest that the D1 receptor is involved in memory retrieval, but not memory reconsolidation, processes during extinction of conditioned hyperactivity.

  6. Extinction debt on oceanic islands

    DEFF Research Database (Denmark)

    Triantis, K.A.; Borges, Paulo A. V.; Ladle, R.J.;

    2010-01-01

    the magnitude of such future extinction events has been hampered by potentially inaccurate assumptions about the slope of species-area relationships, which are habitat- and taxon-specific. We overcome this challenge by applying a method that uses the historical sequence of deforestation in the Azorean Islands...

  7. A model of mass extinction

    CERN Document Server

    Newman, M E J

    1997-01-01

    A number of authors have in recent years proposed that the processes of macroevolution may give rise to self-organized critical phenomena which could have a significant effect on the dynamics of ecosystems. In particular it has been suggested that mass extinction may arise through a purely biotic mechanism as the result of so-called coevolutionary avalanches. In this paper we first explore the empirical evidence which has been put forward in favor of this conclusion. The data center principally around the existence of power-law functional forms in the distribution of the sizes of extinction events and other quantities. We then propose a new mathematical model of mass extinction which does not rely on coevolutionary effects and in which extinction is caused entirely by the action of environmental stresses on species. In combination with a simple model of species adaptation we show that this process can account for all the observed data without the need to invoke coevolution and critical processes. The model al...

  8. Interstellar Extinction by Spheroidal Dust Grains

    OpenAIRE

    Gupta, Ranjan; Mukai, Tadashi; Vaidya, D. B.; Sen, Asoke K.; Okada, Yasuhiko

    2005-01-01

    Observations of interstellar extinction and polarization indicate that the interstellar medium consists of aligned non-spherical dust grains which show variation in the interstellar extinction curve for wavelengths ranging from NIR to UV. To model the extinction and polarization, one cannot use the Mie theory which assumes the grains as solid spheres. We have used a T-matrix based method for computing the extinction efficiencies of spheroidal silicate and graphite grains of different shapes (...

  9. D-cycloserine and the facilitation of extinction of conditioned fear: consequences for reinstatement.

    Science.gov (United States)

    Ledgerwood, Lana; Richardson, Rick; Cranney, Jacquelyn

    2004-06-01

    Several recent studies have reported that D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist, facilitates extinction of learned fear in rats. Other studies have shown that representation of the unconditioned stimulus (US) can reinstate learned fear after extinction. This study examined whether this reinstatement effect occurs in Sprague-Dawley rats given DCS at the time of extinction. Results showed that saline-treated rats exhibited the reinstatement effect but DCS-treated rats did not (Experiments 1 and 2). This lack of reinstatement in DCS-treated rats was not due to residual effects of DCS on either US or context processing (Experiment 3). Overall, these results (a) raise questions about the mechanisms underlying DCS facilitation of extinction and (b) suggest that DCS might have substantial practical benefit.

  10. Savings and extinction of conditioned eyeblink responses in fragile X syndrome

    DEFF Research Database (Denmark)

    Smit, A E; van der Geest, J N; Vellema, M

    2008-01-01

    with FRAXA. In the present behavioral study, long-term effects of deficiency of FMRP were investigated by examining the acquisition, savings and extinction of delay eyeblink conditioning in male individuals with FRAXA. In the acquisition experiment, subjects with FRAXA displayed a significantly poor...... performance compared with controls. In the savings experiment performed at least 6 months later, subjects with FRAXA and controls showed similar levels of savings of conditioned responses. Subsequently, extinction was faster in subjects with FRAXA than in controls. These findings confirm that absence...... of the FMRP affects cerebellar motor learning. The normal performance in the savings experiment and aberrant performance in the acquisition and extinction experiments of individuals with FRAXA suggest that different mechanisms underlie acquisition, savings and extinction of cerebellar motor learning....

  11. Altered brain activation in a reversal learning task unmasks adaptive changes in cognitive control in writer's cramp

    Directory of Open Access Journals (Sweden)

    Kirsten E. Zeuner

    2016-01-01

    The Brodmann area 32 (BA32 is part of the dorsal anterior cingulate cortex (dACC that plays an important role in coordinating and integrating information to guide behavior and in reward-based learning. The dACC is connected with the basal ganglia-thalamo-loop modulated by dopaminergic signaling. This finding suggests disturbed integration of reinforcement history in decision making and implicate that the reward system might contribute to the pathogenesis in writer's cramp.

  12. Interactions between procedural learning and cocaine exposure alter spontaneous and cortically-evoked spike activity in the dorsal striatum

    Directory of Open Access Journals (Sweden)

    Janie eOndracek

    2010-12-01

    Full Text Available We have previously shown that cocaine enhances gene regulation in the sensorimotor striatum associated with procedural learning in a running-wheel paradigm. Here we assessed whether cocaine produces enduring modifications of learning-related changes in striatal neuron activity, using single-unit recordings in anesthetized rats 1 day after the wheel training. Spontaneous and cortically-evoked spike activity was compared between groups treated with cocaine or vehicle immediately prior to the running-wheel training or placement in a locked wheel (control conditions. We found that wheel training in vehicle-treated rats increased the average firing rate of spontaneously active neurons without changing the relative proportion of active to quiescent cells. In contrast, in rats trained under the influence of cocaine, the proportion of spontaneously firing to quiescent cells was significantly greater than in vehicle-treated, trained rats. However, this effect was associated with a lower average firing rate in these spontaneously active cells, suggesting that training under the influence of cocaine recruited additional low-firing cells. Measures of cortically-evoked activity revealed a second interaction between cocaine treatment and wheel training, namely, a cocaine-induced decrease in spike onset latency in control rats (locked wheel. This facilitatory effect of cocaine was abolished when rats trained in the running wheel during cocaine action. These findings highlight important interactions between cocaine and procedural learning, which act to modify population firing activity and the responsiveness of striatal neurons to excitatory inputs. Moreover, these effects were found 24 hours after the training and last drug exposure indicating that cocaine exposure during the learning phase triggers long-lasting changes in synaptic plasticity in the dorsal striatum. Such changes may contribute to the transition from recreational to habitual or compulsive drug

  13. Uncertainty-Dependent Extinction of Fear Memory in an Amygdala-mPFC Neural Circuit Model

    Science.gov (United States)

    Li, Yuzhe; Nakae, Ken; Ishii, Shin; Naoki, Honda

    2016-01-01

    Uncertainty of fear conditioning is crucial for the acquisition and extinction of fear memory. Fear memory acquired through partial pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US) is more resistant to extinction than that acquired through full pairings; this effect is known as the partial reinforcement extinction effect (PREE). Although the PREE has been explained by psychological theories, the neural mechanisms underlying the PREE remain largely unclear. Here, we developed a neural circuit model based on three distinct types of neurons (fear, persistent and extinction neurons) in the amygdala and medial prefrontal cortex (mPFC). In the model, the fear, persistent and extinction neurons encode predictions of net severity, of unconditioned stimulus (US) intensity, and of net safety, respectively. Our simulation successfully reproduces the PREE. We revealed that unpredictability of the US during extinction was represented by the combined responses of the three types of neurons, which are critical for the PREE. In addition, we extended the model to include amygdala subregions and the mPFC to address a recent finding that the ventral mPFC (vmPFC) is required for consolidating extinction memory but not for memory retrieval. Furthermore, model simulations led us to propose a novel procedure to enhance extinction learning through re-conditioning with a stronger US; strengthened fear memory up-regulates the extinction neuron, which, in turn, further inhibits the fear neuron during re-extinction. Thus, our models increased the understanding of the functional roles of the amygdala and vmPFC in the processing of uncertainty in fear conditioning and extinction. PMID:27617747

  14. From the neurobiology of extinction to improved clinical treatments.

    Science.gov (United States)

    Morrison, Filomene G; Ressler, Kerry J

    2014-04-01

    The neural circuitry underlying the fear response is extremely well conserved across mammalian species, which has allowed for the rapid translation of research findings in rodent models of fear to therapeutic interventions in human populations. Many aspects of exposure-based psychotherapy treatments in humans, which are widely used in the treatment of PTSD, panic disorder, phobias, and other anxiety disorders, are closely paralleled by extinction training in rodent fear conditioning models. Here, we discuss how the neural circuitry of fear learning and extinction in rodent animal models may be used to understand the underlying neural circuitry of fear-related disorders, such as PTSD in humans. We examine the factors that contribute to the pathology and development of PTSD. Next, we will review how fear is measured in animal models using classical Pavlovian fear conditioning paradigms, as well as brain regions such as the amygdala, which are involved in the fear response across species. Finally, we highlight the following three systems involved in the extinction of fear, all of which represent promising avenues for therapeutic interventions in the clinic: (1) the role of the glutamatergic N-methyl-d-aspartate (NMDA) receptor, (2) the role of the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) induced signaling pathway, and (3) the role of the renin-angiotensin system. The modulation of pathways underlying fear learning and extinction, such as the ones presented in this review, in combination with extinction-based exposure therapy, represents promising avenues for therapeutic intervention in the treatment of human fear related disorders.

  15. From lab to clinic: Extinction of cued cravings to reduce overeating.

    Science.gov (United States)

    Jansen, Anita; Schyns, Ghislaine; Bongers, Peggy; van den Akker, Karolien

    2016-08-01

    Food cue reactivity is a strong motivation to eat, even in the absence of hunger. Therefore, food cue reactivity might sabotage healthy eating, induce weight gain and impede weight loss or weight maintenance. Food cue reactivity can be learned via Pavlovian appetitive conditioning: It is easily acquired but the extinction of appetitive responding seems to be more challenging. Several properties of extinction make it fragile: extinction does not erase the original learning and extinction is context-dependent. These properties threaten full extinction and increase the risk of full relapse. Extinction procedures are discussed to reduce or prevent the occurrence of rapid reacquisition, spontaneous recovery, renewal and reinstatement after extinction. A translation to food cue exposure treatment is made and suggestions are provided, such as conducting the exposure in relevant contexts, using occasional reinforcement and targeting expectancy violation instead of habituation. A new hypothesis proposed here is that the adding of inhibition training to strengthen inhibition skills that reduce instrumental responding, might be beneficial to improve food cue exposure effects.

  16. The Class I HDAC Inhibitor RGFP963 Enhances Consolidation of Cued Fear Extinction

    Science.gov (United States)

    Bowers, Mallory E.; Xia, Bing; Carreiro, Samantha; Ressler, Kerry J.

    2015-01-01

    Evidence indicates that broad, nonspecific histone deacetylase (HDAC) inhibition enhances learning and memory, however, the contribution of the various HDACs to specific forms of learning is incompletely understood. Here, we show that the Class I HDAC inhibitor, RGFP963, enhances consolidation of cued fear extinction. However, RGFP966, a strong…

  17. Further Evidence of Auditory Extinction in Aphasia

    Science.gov (United States)

    Marshall, Rebecca Shisler; Basilakos, Alexandra; Love-Myers, Kim

    2013-01-01

    Purpose: Preliminary research ( Shisler, 2005) suggests that auditory extinction in individuals with aphasia (IWA) may be connected to binding and attention. In this study, the authors expanded on previous findings on auditory extinction to determine the source of extinction deficits in IWA. Method: Seventeen IWA (M[subscript age] = 53.19 years)…

  18. Determining Extinction Ratio Of A Laser Diode

    Science.gov (United States)

    Unger, Glenn L.

    1992-01-01

    Improved technique to determine extinction ratio of pulsed laser diode based partly on definition of extinction ratio applicable to nonideal laser pulses. Heretofore, determinations involved assumption of ideal laser pulses, and neglected optical power from background light. Because power fluctuates during real pulse, more realistic to define extinction ratio in terms of energy obtained.

  19. Fear conditioning and extinction across development: evidence from human studies and animal models.

    Science.gov (United States)

    Shechner, Tomer; Hong, Melanie; Britton, Jennifer C; Pine, Daniel S; Fox, Nathan A

    2014-07-01

    The ability to differentiate danger and safety through associative processes emerges early in life. Understanding the mechanisms underlying associative learning of threat and safety can clarify the processes that shape development of normative fears and pathological anxiety. Considerable research has used fear conditioning and extinction paradigms to delineate underlying mechanisms in animals and human adults; however, little is known about these mechanisms in children and adolescents. The current paper summarizes the empirical data on the development of fear conditioning and extinction. It reviews methodological considerations and future directions for research on fear conditioning and extinction in pediatric populations.

  20. Inhibition of Spontaneous Recovery of Fear by mGluR5 after Prolonged Extinction Training

    OpenAIRE

    Sheng-Chun Mao; Chih-Hua Chang; Chia-Chen Wu; M Juliana Orejarena; Manzoni, Olivier J.; Po-Wu Gean

    2013-01-01

    Fear behavior is vital for survival and involves learning contingent associations of non-threatening cues with aversive stimuli. In contrast, excessive levels of fear can be maladaptive and lead to anxiety disorders. Generally, extensive sessions of extinction training correlates with reduced spontaneous recovery. The molecular mechanisms underlying the long-term inhibition of fear recovery following repeated extinction training are not fully understood. Here we show that in rats, prolonged e...

  1. Effects of recent environmental change on accuracy of inferences of extinction status.

    Science.gov (United States)

    Clements, Christopher F; Collen, Ben; Blackburn, Tim M; Petchey, Owen L

    2014-08-01

    Correctly classifying a species as extinct or extant is of critical importance if current rates of biodiversity loss are to be accurately quantified. Observing an extinction event is rare, so in many cases extinction status is inferred using methods based on the analysis of records of historic sighting events. The accuracy of such methods is difficult to test. However, results of recent experiments with microcosm communities suggest that the rate at which a population declines to extinction, potentially driven by varying environmental conditions, may alter one's ability accurately to infer extinction status. We tested how the rate of population decline, driven by historic environmental change, alters the accuracy of 6 commonly applied sighting-based methods used to infer extinction. We used data from small-scale experimental communities and recorded wild population extirpations. We assessed how accuracy of the different methods was affected by rate of population decline, search effort, and number of sighting events recorded. Rate of population decline and historic population size of the species affected the accuracy of inferred extinction dates; however, faster declines produced more accurate inferred dates of extinction, but only when population sizes were higher. Optimal linear estimation (OLE) offered the most reliable and robust estimates, though no single method performed best in all situations, and it may be appropriate to use a different method if information regarding historic search efforts is available. OLE provided the most accurate estimates of extinction when the number of sighting events used was >10, and future use of this method should take this into account. Data from experimental populations provide added insight into testing techniques to discern wild extirpation events. Care should be taken designing such experiments so that they mirror closely the abundance dynamics of populations affected by real-world extirpation events.

  2. Development of Extinction Imagers for the Determination of Atmospheric Optical Extinction

    Science.gov (United States)

    2014-08-01

    extinction coefficient > 0.4 km" ), the transmissometer tends to report higher values than the MSI. There are two possible reasons for this behavior ...REPORT TYPE Final Report 4. TITLE AND SUBTITLE Development of Extinction Imagers for the Determination of Atmospheric Optical Extinction 6. AUTHOR...further develop Extinction Imagers for use in the ocean environment, and to extend the capabilities into the Short Wave IR (SWIR). Extinction Imaging

  3. Inhibiting corticosterone synthesis during fear memory formation exacerbates cued fear extinction memory deficits within the single prolonged stress model.

    Science.gov (United States)

    Keller, Samantha M; Schreiber, William B; Stanfield, Briana R; Knox, Dayan

    2015-01-01

    Using the single prolonged stress (SPS) animal model of post-traumatic stress disorder (PTSD), previous studies suggest that enhanced glucocorticoid receptor (GR) expression leads to cued fear extinction retention deficits. However, it is unknown how the endogenous ligand of GRs, corticosterone (CORT), may contribute to extinction retention deficits in the SPS model. Given that CORT synthesis during fear learning is critical for fear memory consolidation and SPS enhances GR expression, CORT synthesis during fear memory formation could strengthen fear memory in SPS rats by enhancing GR activation during fear learning. In turn, this could lead to cued fear extinction retention deficits. We tested the hypothesis that CORT synthesis during fear learning leads to cued fear extinction retention deficits in SPS rats by administering the CORT synthesis inhibitor metyrapone to SPS and control rats prior to fear conditioning, and observed the effect this had on extinction memory. Inhibiting CORT synthesis during fear memory formation in control rats tended to decrease cued freezing, though this effect never reached statistical significance. Contrary to our hypothesis, inhibiting CORT synthesis during fear memory formation disrupted extinction retention in SPS rats. This finding suggests that even though SPS exposure leads to cued fear extinction memory deficits, CORT synthesis during fear memory formation enhances extinction retention in SPS rats. This suggests that stress-induced CORT synthesis in previously stressed rats can be beneficial.

  4. Kainate-induced epileptogenesis alters circular hole board learning strategy but not the performance of C57BL/6J mice.

    Science.gov (United States)

    Hubens, Chantal J; Kaptein, Pascale S; ter Horst, Judith P; Voskuyl, Rob A; Schenk, Geert J

    2014-12-01

    Patients with mesial temporal lobe epilepsy (mTLE) frequently show cognitive deficits. However, the relation between mTLE and cognitive impairment is poorly understood. To gain more insight into epilepsy-associated alterations in cognitive performance, we studied the spatial learning of C57BL/6J mice five weeks after kainate-induced status epilepticus (SE). Typically, structural hippocampal rearrangements take place within five weeks after SE. Mice were monitored by exposing them to four tasks with a focus on spatial memory and anxiety: the circular hole board, modified hole board, novel object-placement task, and elevated plus maze. On the circular hole board, animals showed a higher preference for hippocampus-independent strategies after SE. In contrast, no change in strategy was seen on the modified hole board, but animals with SE were able to finish the task more often. Animals did not have an increased preference for a relocated object in the novel object-placement task but showed an increased locomotion after SE. No indications for altered anxiety were found when tested on the elevated plus maze following SE. These data suggest that the circular hole board is a well-suited paradigm to detect subtle SE-induced hippocampal deficits.

  5. Neanderthal extinction by competitive exclusion.

    Directory of Open Access Journals (Sweden)

    William E Banks

    Full Text Available BACKGROUND: Despite a long history of investigation, considerable debate revolves around whether Neanderthals became extinct because of climate change or competition with anatomically modern humans (AMH. METHODOLOGY/PRINCIPAL FINDINGS: We apply a new methodology integrating archaeological and chronological data with high-resolution paleoclimatic simulations to define eco-cultural niches associated with Neanderthal and AMH adaptive systems during alternating cold and mild phases of Marine Isotope Stage 3. Our results indicate that Neanderthals and AMH exploited similar niches, and may have continued to do so in the absence of contact. CONCLUSIONS/SIGNIFICANCE: The southerly contraction of Neanderthal range in southwestern Europe during Greenland Interstadial 8 was not due to climate change or a change in adaptation, but rather concurrent AMH geographic expansion appears to have produced competition that led to Neanderthal extinction.

  6. The dynamics of conditioning and extinction.

    Science.gov (United States)

    Killeen, Peter R; Sanabria, Federico; Dolgov, Igor

    2009-10-01

    Pigeons responded to intermittently reinforced classical conditioning trials with erratic bouts of responding to the conditioned stimulus. Responding depended on whether the prior trial contained a peck, food, or both. A linear persistence-learning model moved pigeons into and out of a response state, and a Weibull distribution for number of within-trial responses governed in-state pecking. Variations of trial and intertrial durations caused correlated changes in rate and probability of responding and in model parameters. A novel prediction--in the protracted absence of food, response rates can plateau above zero--was validated. The model predicted smooth acquisition functions when instantiated with the probability of food but a more accurate jagged learning curve when instantiated with trial-to-trial records of reinforcement. The Skinnerian parameter was dominant only when food could be accelerated or delayed by pecking. These experiments provide a framework for trial-by-trial accounts of conditioning and extinction that increases the information available from the data, permitting such accounts to comment more definitively on complex contemporary models of momentum and conditioning.

  7. Quantification of extinction mechanism in counterflow premixed flames

    KAUST Repository

    Choi, Sangkyu

    2014-09-01

    The extinction mechanisms of stretched premixed flames have been investigated numerically for the fuels of CH4, C3H8, H2, CO and for the mixture fuels of CH4+H2 and CO+H2 by adopting symmetric double premixed flames in a counterflow configuration. The local equilibrium temperature concept was used as a measure of energy loss or gain in order to quantify the extinction mechanism by preferential diffusion and/or incomplete reaction. The energy loss ratio from preferential diffusion arising from non-unity Lewis number and the loss ratio from incomplete reaction were calculated at various equivalence ratios near flame extinction. The results showed that the extinction of lean H2, CH4, CH4+H2, CO+H2, and rich C3H8 premixed flames was caused by incomplete reaction due to insufficient reaction time, indicating that the effective Lewis number was smaller than unity, while the effect of preferential diffusion resulted in energy gain. However, the extinction of rich H2, CH4, CH4+H2, CO+H2, and lean C3H8 premixed flames was affected by the combined effects of preferential diffusion and incomplete reaction indicating that the effective Lewis number was larger than unity. In CO premixed flames, incomplete reaction was dominant in both lean and rich cases due to the effective Lewis number close to unity. The effect of H2 mixing to CO is found to be quite significant as compared to CH4+H2 cases, which can alter the flame behavior of CO flames to that of H2.

  8. Effects of cycloheximide on extinction in an appetitively motivated operant conditioning task depend on re-exposure duration.

    Science.gov (United States)

    Mierzejewski, Pawel; Olczak, Mieszko; Rogowski, Artur; Kostowski, Wojciech; Samochowiec, Jerzy; Filip, Malgorzata; Przegalinski, Edmund; Bienkowski, Przemyslaw

    2008-08-29

    Little is known about the role of new protein synthesis in extinction of operant responding for natural and chemical reinforcers. In the present study, the authors investigated whether the effects of a protein synthesis inhibitor, cycloheximide (CHX) on extinction of operant responding for sweet reward depended on the duration of re-exposure sessions. In addition, the authors investigated whether the effects of CHX on extinction could generalize to relapse of saccharin seeking induced by discrete cues. CHX injected after short re-exposure sessions (5min) accelerated extinction of non-reinforced responding. In contrast, the drug injected after long re-exposure sessions (30min) partially inhibited extinction. Reinstatement of saccharin seeking induced by the saccharin-paired discrete cues was not altered by the previous treatment with CHX. Concluding, the results of the present study indicate that: (i) the protein synthesis inhibitor, CHX can alter extinction of operant responding for sweet reward in rats; (ii) the effects of CHX on extinction critically depend on the duration of re-exposure/extinction sessions and do not generalize to relapse of saccharin seeking induced by discrete cues.

  9. Revisiting propranolol and PTSD: Memory erasure or extinction enhancement?

    Science.gov (United States)

    Giustino, Thomas F; Fitzgerald, Paul J; Maren, Stephen

    2016-04-01

    Posttraumatic stress disorder (PTSD) has been described as the only neuropsychiatric disorder with a known cause, yet effective behavioral and pharmacotherapies remain elusive for many afflicted individuals. PTSD is characterized by heightened noradrenergic signaling, as well as a resistance to extinction learning. Research aimed at promoting more effective treatment of PTSD has focused on memory erasure (disrupting reconsolidation) and/or enhancing extinction retention through pharmacological manipulations. Propranolol, a β-adrenoceptor antagonist, has received considerable attention for its therapeutic potential in PTSD, although its impact on patients is not always effective. In this review, we briefly examine the consequences of β-noradrenergic manipulations on both reconsolidation and extinction learning in rodents and in humans. We suggest that propranolol is effective as a fear-reducing agent when paired with behavioral therapy soon after trauma when psychological stress is high, possibly preventing or dampening the later development of PTSD. In individuals who have already suffered from PTSD for a significant period of time, propranolol may be less effective at disrupting reconsolidation of strong fear memories. Also, when PTSD has already developed, chronic treatment with propranolol may be more effective than acute intervention, given that individuals with PTSD tend to experience long-term, elevated noradrenergic hyperarousal.

  10. Extinction reveals that primary sensory cortex predicts reinforcement outcome.

    Science.gov (United States)

    Bieszczad, Kasia M; Weinberger, Norman M

    2012-02-01

    Primary sensory cortices are traditionally regarded as stimulus analysers. However, studies of associative learning-induced plasticity in the primary auditory cortex (A1) indicate involvement in learning, memory and other cognitive processes. For example, the area of representation of a tone becomes larger for stronger auditory memories and the magnitude of area gain is proportional to the degree that a tone becomes behaviorally important. Here, we used extinction to investigate whether 'behavioral importance' specifically reflects a sound's ability to predict reinforcement (reward or punishment) vs. to predict any significant change in the meaning of a sound. If the former, then extinction should reverse area gains as the signal no longer predicts reinforcement. Rats (n = 11) were trained to bar-press to a signal tone (5.0 kHz) for water-rewards, to induce signal-specific area gains in A1. After subsequent withdrawal of reward, A1 was mapped to determine representational areas. Signal-specific area gains, estimated from a previously established brain-behavior quantitative function, were reversed, supporting the 'reinforcement prediction' hypothesis. Area loss was specific to the signal tone vs. test tones, further indicating that withdrawal of reinforcement, rather than unreinforced tone presentation per se, was responsible for area loss. Importantly, the amount of area loss was correlated with the amount of extinction (r = 0.82, P reinforcement, and that the number of cells tuned to a stimulus can dictate its ability to command behavior.

  11. The hypocretin/orexin system mediates the extinction of fear memories.

    Science.gov (United States)

    Flores, África; Valls-Comamala, Victòria; Costa, Giulia; Saravia, Rocío; Maldonado, Rafael; Berrendero, Fernando

    2014-11-01

    Anxiety disorders are often associated with an inability to extinguish learned fear responses. The hypocretin/orexin system is involved in the regulation of emotional states and could also participate in the consolidation and extinction of aversive memories. Using hypocretin receptor-1 and hypocretin receptor-2 antagonists, hypocretin-1 and hypocretin-2 peptides, and hypocretin receptor-1 knockout mice, we investigated the role of the hypocretin system in cue- and context-dependent fear conditioning and extinction. Hypocretins were crucial for the consolidation of fear conditioning, and this effect was mainly observed in memories with a high emotional component. Notably, after the acquisition of fear memory, hypocretin receptor-1 blockade facilitated fear extinction, whereas hypocretin-1 administration impaired this extinction process. The extinction-facilitating effects of the hypocretin receptor-1 antagonist SB334867 were associated with increased expression of cFos in the basolateral amygdala and the infralimbic cortex. Intra-amygdala, but neither intra-infralimbic prefrontal cortex nor intra-dorsohippocampal infusion of SB334867 enhanced fear extinction. These results reveal a key role for hypocretins in the extinction of aversive memories and suggest that hypocretin receptor-1 blockade could represent a novel therapeutic target for the treatment of diseases associated with inappropriate retention of fear, such as post-traumatic stress disorder and phobias.

  12. Extinction and reinstatement of phasic dopamine signals in the nucleus accumbens core during Pavlovian conditioning.

    Science.gov (United States)

    Sunsay, Ceyhun; Rebec, George V

    2014-10-01

    The prediction-error model of dopamine (DA) signaling has largely been confirmed with various appetitive Pavlovian conditioning procedures and has been supported in tests of Pavlovian extinction. Studies have repeatedly shown, however, that extinction does not erase the original memory of conditioning as the prediction-error model presumes, putting the model at odds with contemporary views that treat extinction as an episode of learning rather than unlearning of conditioning. Here, we combined fast-scan cyclic voltammetry (FSCV) with appetitive Pavlovian conditioning to assess DA release directly during extinction and reinstatement. DA was monitored in the nucleus accumbens core, which plays a key role in reward processing. Following at least 4 daily sessions of 16 tone-food pairings, fast-scan cyclic voltammetry was performed while rats received additional tone-food pairings followed by tone alone presentations (i.e., extinction). Acquisition memory was reinstated with noncontingent presentations of reward and then tested with cue presentation. Tone-food pairings produced transient (1- to 3-s) DA release in response to tone. During extinction, the amplitude of the DA response decreased significantly. Following presentation of 2 noncontingent food pellets, subsequent tone presentation reinstated the DA signal. Our results support the prediction-error model for appetitive Pavlovian extinction but not for reinstatement.

  13. Extinction of goal tracking also eliminates the conditioned reinforcing effects of an appetitive conditioned stimulus.

    Science.gov (United States)

    Kearns, David N; Tunstall, Brendan J; Marks, Katherine R; Weiss, Stanley J

    2012-02-01

    Previous studies have suggested that the effects of extinction are response-specific. The present study investigated whether an extinction treatment that eliminated goal tracking elicited by an appetitive conditioned stimulus (CS) would also eliminate the conditioned reinforcing effects of that CS. Rats were first trained on a goal-tracking procedure in which an auditory CS was paired with a food unconditioned stimulus. Animals learned to approach the location where the food was delivered. In a subsequent phase, rats in one group received extinction training that eliminated the goal-tracking elicited by the CS. Rats in the other group did not experience extinction of the food-paired CS. Then, both groups received a test for conditioned reinforcement in which leverpresses resulted in the brief presentation of the stimulus previously paired with food. This stimulus did not act as a conditioned reinforcer in the group that had been subjected to extinction training, but did serve as a conditioned reinforcer in the group that did not experience extinction. These results indicate that the effects of extinction generalize from the approach-eliciting to the conditioned reinforcing effects of an appetitive CS.

  14. Sex differences in learning processes of classical and operant conditioning.

    Science.gov (United States)

    Dalla, Christina; Shors, Tracey J

    2009-05-25

    Males and females learn and remember differently at different times in their lives. These differences occur in most species, from invertebrates to humans. We review here sex differences as they occur in laboratory rodent species. We focus on classical and operant conditioning paradigms, including classical eyeblink conditioning, fear-conditioning, active avoidance and conditioned taste aversion. Sex differences have been reported during acquisition, retention and extinction in most of these paradigms. In general, females perform better than males in the classical eyeblink conditioning, in fear-potentiated startle and in most operant conditioning tasks, such as the active avoidance test. However, in the classical fear-conditioning paradigm, in certain lever-pressing paradigms and in the conditioned taste aversion, males outperform females or are more resistant to extinction. Most sex differences in conditioning are dependent on organizational effects of gonadal hormones during early development of the brain, in addition to modulation by activational effects during puberty and adulthood. Critically, sex differences in performance account for some of the reported effects on learning and these are discussed throughout the review. Because so many mental disorders are more prevalent in one sex than the other, it is important to consider sex differences in learning when applying animal models of learning for these disorders. Finally, we discuss how sex differences in learning continue to alter the brain throughout the lifespan. Thus, sex differences in learning are not only mediated by sex differences in the brain, but also contribute to them.

  15. Fear conditioning and extinction in anxiety- and depression-prone persons.

    Science.gov (United States)

    Dibbets, Pauline; van den Broek, Anne; Evers, Elisabeth A T

    2015-01-01

    Anxiety and depression frequently co-occur and may share similar deficits in the processing of emotional stimuli. High anxiety is associated with a failure in the acquisition and extinction of fear conditioning. Despite the supposed common deficits, no research has been conducted on fear acquisition and extinction in depression. The main aim of the present study was to investigate and compare fear acquisition and extinction in anxiety- and depression-prone participants. Non-clinical anxious, depressive, anxious-depressive and control participants performed a fear discrimination task. During acquisition, the CS+ predicted an aversive event (unconditioned stimulus, US) and the CS- safety (no US). During extinction, the CS+ was no longer followed by the US, rendering it (temporarily) into a safety signal. On each CS participants rated their US expectancy; skin conductance responses (SCRs) were measured throughout. The expectancy scores indicated that high anxiety resulted in less safety learning during acquisition and extinction; no effect of depression was observed. SCRs showed that high-anxiety persons displayed less discrimination learning (CS+ minus CS-) during acquisition than low-anxiety persons. During extinction, high-depression persons demonstrated more discriminative SCR than low-depression persons. The observed discrepancies in response patterns of high-anxiety and -depression persons seem to indicate distinctive information processing of emotional stimuli.

  16. Controlled cortical impact before or after fear conditioning does not affect fear extinction in mice.

    Science.gov (United States)

    Sierra-Mercado, Demetrio; McAllister, Lauren M; Lee, Christopher C H; Milad, Mohammed R; Eskandar, Emad N; Whalen, Michael J

    2015-05-01

    Post-traumatic stress disorder (PTSD) is characterized in part by impaired extinction of conditioned fear. Traumatic brain injury (TBI) is thought to be a risk factor for development of PTSD. We tested the hypothesis that controlled cortical impact (CCI) would impair extinction of fear learned by Pavlovian conditioning, in mice. To mimic the scenarios in which TBI occurs prior to or after exposure to an aversive event, severe CCI was delivered to the left parietal cortex at one of two time points: (1) Prior to fear conditioning, or (2) after conditioning. Delay auditory conditioning was achieved by pairing a tone with a foot shock in "context A". Extinction training involved the presentation of tones in a different context (context B) in the absence of foot shock. Test for extinction memory was achieved by presentation of additional tones alone in context B over the following two days. In pre- or post-injury paradigms, CCI did not influence fear learning and extinction. Furthermore, CCI did not affect locomotor activity or elevated plus maze testing. Our results demonstrate that, within the time frame studied, CCI does not impair the acquisition and expression of conditioned fear or extinction memory.

  17. Compound stimulus presentation and the norepinephrine reuptake inhibitor atomoxetine enhance long-term extinction of cocaine-seeking behavior.

    Science.gov (United States)

    Janak, Patricia H; Bowers, M Scott; Corbit, Laura H

    2012-03-01

    Drug abstinence is frequently compromised when addicted individuals are re-exposed to environmental stimuli previously associated with drug use. Research with human addicts and in animal models has demonstrated that extinction learning (non-reinforced cue-exposure) can reduce the capacity of such stimuli to induce relapse, yet extinction therapies have limited long-term success under real-world conditions (Bouton, 2002; O'Brien, 2008). We hypothesized that enhancing extinction would reduce the later ability of drug-predictive cues to precipitate drug-seeking behavior. We, therefore, tested whether compound stimulus presentation and pharmacological treatments that augment noradrenergic activity (atomoxetine; norepinephrine reuptake inhibitor) during extinction training would facilitate the extinction of drug-seeking behaviors, thus reducing relapse. Rats were trained that the presentation of a discrete cue signaled that a lever press response would result in cocaine reinforcement. Rats were subsequently extinguished and spontaneous recovery of drug-seeking behavior following presentation of previously drug-predictive cues was tested 4 weeks later. We find that compound stimulus presentations or pharmacologically increasing noradrenergic activity during extinction training results in less future recovery of responding, whereas propranolol treatment reduced the benefit seen with compound stimulus presentation. These data may have important implications for understanding the biological basis of extinction learning, as well as for improving the outcome of extinction-based therapies.

  18. A lesson in defining "extinct"

    OpenAIRE

    Asimow, Paul D.

    2014-01-01

    Toni Feder’s Issues and Events news item about the High-Altitude Water Cherenkov Gamma-Ray Observatory under construction in Mexico ( Physics Today, October 2013, page 22) begins by describing the site as “nestled at 4100 m on the slopes of Sierra Negra, an extinct volcano.” However, as the picture accompanying her piece or a cursory examination in Google Earth makes clear, the site is not on the slopes of Sierra Negra. It sits in the saddle between Sierra Negra and its much larger companion ...

  19. Extinction Maps in the WFAU Archives

    CERN Document Server

    Cross, Nicholas

    2015-01-01

    A brief set of notes about the database design for 3D maps of dust extinction in the WFAU Archives, which support data from UKIRT-WFCAM, VISTA and VST. The notes also detail typical use cases, such as getting colour-excesses, extinction-corrections, spectral energy distributions and colour-magnitude diagrams and demonstrate the SQL queries to return data, along with examples from VVV DR2 with bulge extinction maps from Chen et al. (2013).

  20. Extinction by the long dielectric needles

    CERN Document Server

    Cherkas, Nadejda L

    2016-01-01

    Electromagnetic wave extinction by the very long but finite dielectric needle is compared with that by the infinite dielectric cylinder for an oblique incidence of the electromagnetic wave. It is shown that the renormalized Hankel functions without the logarithmic terms should be used for the calculation of the extinction per unit length of the infinite dielectric cylinder to apply it for extinction calculations by the finite dielectric cylinder.

  1. The Astronomical Pulse of Global Extinction Events

    Directory of Open Access Journals (Sweden)

    David F.V. Lewis

    2006-01-01

    Full Text Available The linkage between astronomical cycles and the periodicity of mass extinctions is reviewed and discussed. In particular, the apparent 26 million year cycle of global extinctions may be related to the motion of the solar system around the galaxy, especially perpendicular to the galactic plane. The potential relevance of Milankovitch cycles is also explored in the light of current evidence for the possible causes of extinction events over a geological timescale.

  2. The astronomical pulse of global extinction events.

    Science.gov (United States)

    Lewis, David F V; Dorne, Jean-Lou C M

    2006-06-23

    The linkage between astronomical cycles and the periodicity of mass extinctions is reviewed and discussed. In particular, the apparent 26 million year cycle of global extinctions may be related to the motion of the solar system around the galaxy, especially perpendicular to the galactic plane. The potential relevance of Milankovitch cycles is also explored in the light of current evidence for the possible causes of extinction events over a geological timescale.

  3. Mass Extinctions vs. Uniformitarianism in Biological Evolution

    OpenAIRE

    Bak, Per; Paczuski, Maya

    1996-01-01

    It is usually believed that Darwin's theory leads to a smooth gradual evolution, so that mass extinctions must be caused by external shocks. However, it has recently been argued that mass extinctions arise from the intrinsic dynamics of Darwinian evolution. Species become extinct when swept by intermittent avalanches propagating through the global ecology. These ideas are made concrete through studies of simple mathematical models of coevolving species. The models exhibit self-organized criti...

  4. Resistance to extinction and behavioral momentum

    OpenAIRE

    Nevin, John A.

    2012-01-01

    In the metaphor of behavioral momentum, reinforcement is assumed to strengthen discriminated operant behavior in the sense of increasing its resistance to disruption, and extinction is viewed as disruption by contingency termination and reinforcer omission. In multiple schedules of intermittent reinforcement, resistance to extinction is an increasing function of reinforcer rate, consistent with a model based on the momentum metaphor. The partial-reinforcement extinction effect, which opposes ...

  5. Acquisition, Extinction, Recovery, and Reversal of Different Response Sequences Under Conditional Control by Nicotine in Rats

    Science.gov (United States)

    Troisi, Joseph R.

    2013-01-01

    Complex voluntary behaviors occur in sequence. Eight rats were trained in an operant procedure that used nicotine and non-drug (saline) states as interoceptive cues that signaled which of two behavioral sequences led to food reward. The distal and proximal responses in the chain were always maintained on variable interval 30-sec and fixed ratio-1 schedules, respectively, and rate differences between the responses were used as the dependent variable. Extinction and reversal training was conducted. Distal response rates were significantly greater than proximal response rates during training, testing, extinction, and reversal learning. These data suggest that (a) nicotine can establish interoceptive control over different response sequences, and (b) extinction of one response sequence may be state-dependent. The clinical relevance of extinction of complex behavioral repertoires such as drug-seeking and drug-taking behavior that are evoked by specific interoceptive cues is addressed in regard to drug abuse treatment and relapse. PMID:24837654

  6. Enhancing Divergent Search through Extinction Events

    DEFF Research Database (Denmark)

    Lehman, Joel; Miikkulainen, Risto

    2015-01-01

    A challenge in evolutionary computation is to create representations as evolvable as those in natural evolution. This paper hypothesizes that extinction events, i.e. mass extinctions, can significantly increase evolvability, but only when combined with a divergent search algorithm, i.e. a search...... for the capacity to evolve. This hypothesis is tested through experiments in two evolutionary robotics domains. The results show that combining extinction events with divergent search increases evolvability, while combining them with convergent search offers no similar benefit. The conclusion is that extinction...... events may provide a simple and effective mechanism to enhance performance of divergent search algorithms....

  7. Dust Extinction in Compact Planetary Nebulae

    OpenAIRE

    Lee, TH; Kwok, S.

    2005-01-01

    The effects of dust extinction on the departure from axisymmetry in the morphology of planetary nebulae (PNs) are investigated through a comparison of the radio free-free emission and hydrogen recombination line images. The dust extinction maps from five compact PNs are derived using high-resolution (̃0"1) Hα and radio maps of the HST and VLA. These extinction maps are then analyzed by an ellipsoidal shell ionization model including the effects of dust extinction to infer the nebulae's intrin...

  8. Secondary extinction in Pavlovian fear conditioning.

    Science.gov (United States)

    Vurbic, Drina; Bouton, Mark E

    2011-09-01

    Pavlov (1927/1960) reported that following the conditioning of several stimuli, extinction of one conditioned stimulus (CS) attenuated responding to others that had not undergone direct extinction. However, this secondary extinction effect has not been widely replicated in the contemporary literature. In three conditioned suppression experiments with rats, we further explored the phenomenon. In Experiment 1, we asked whether secondary extinction is more likely to occur with target CSs that have themselves undergone some prior extinction. A robust secondary extinction effect was obtained with a nonextinguished target CS. Experiment 2 showed that extinction of one CS was sufficient to reduce renewal of a second CS when it was tested in a neutral (nonextinction) context. In Experiment 3, secondary extinction was observed in groups that initially received intermixed conditioning trials with the target and nontarget CSs, but not in groups that received conditioning of the two CSs in separate sessions. The results are consistent with the hypothesis that CSs must be associated with a common temporal context during conditioning for secondary extinction to occur.

  9. Mass extinctions vs. uniformitarianism in biological evolution

    Energy Technology Data Exchange (ETDEWEB)

    Bak, P.; Paczuski, M.

    1995-12-31

    It is usually believed that Darwin`s theory leads to a smooth gradual evolution, so that mass extinctions must be caused by external shocks. However, it has recently been argued that mass extinctions arise from the intrinsic dynamics of Darwinian evolution. Species become extinct when swept by intermittent avalanches propagating through the global ecology. These ideas are made concrete through studies of simple mathematical models of co-evolving species. The models exhibit self-organized criticality and describe some general features of the extinction pattern in the fossil record.

  10. Climate predictors of late quaternary extinctions

    DEFF Research Database (Denmark)

    Nogués-Bravo, David; Ohlemüller, Ralf; Batra, Persaram

    2010-01-01

    Between 50,000 and 3,000 years before present (BP) 65% of mammal genera weighing over 44 kg went extinct, together with a lower proportion of small mammals. Why species went extinct in such large numbers is hotly debated. One of the arguments proposes that climate changes underlie Late Quaternary...... extinctions, but global quantitative evidence for this hypothesis is still lacking. We test the potential role of global climate change on the extinction of mammals during the Late Quaternary. Our results suggest that continents with the highest climate footprint values, in other words, with climate changes...

  11. Long-term maintenance of immediate or delayed extinction is determined by the extinction-test interval

    OpenAIRE

    Johnson, Justin S.; Escobar, Martha; Kimble, Whitney L.

    2010-01-01

    Short acquisition-extinction intervals (immediate extinction) can lead to either more or less spontaneous recovery than long acquisition-extinction intervals (delayed extinction). Using rat subjects, we observed less spontaneous recovery following immediate than delayed extinction (Experiment 1). However, this was the case only if a relatively long extinction-test interval was used; a relatively short extinction-test interval yielded the opposite result (Experiment 2). Previous data appear co...

  12. Involvement of BDNF signaling transmission from basolateral amygdala to infralimbic prefrontal cortex in conditioned taste aversion extinction.

    Science.gov (United States)

    Xin, Jian; Ma, Ling; Zhang, Tian-Yi; Yu, Hui; Wang, Yue; Kong, Liang; Chen, Zhe-Yu

    2014-05-21

    Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB), play a critical role in memory extinction. However, the detailed role of BDNF in memory extinction on the basis of neural circuit has not been fully understood. Here, we aim to investigate the role of BDNF signaling circuit in mediating conditioned taste aversion (CTA) memory extinction of the rats. We found region-specific changes in BDNF gene expression during CTA extinction. CTA extinction led to increased BDNF gene expression in the basolateral amygdala (BLA) and infralimbic prefrontal cortex (IL) but not in the central amygdaloid nucleus (CeA) and hippocampus (HIP). Moreover, blocking BDNF signaling or exogenous microinjection of BDNF into the BLA or IL could disrupt or enhance CTA extinction, which suggested that BDNF signaling in the BLA and IL is necessary and sufficient for CTA extinction. Interestingly, we found that microinjection of BDNF-neutralizing antibody into the BLA could abolish the extinction training-induced BDNF mRNA level increase in the IL, but not vice versa, demonstrating that BDNF signaling is transmitted from the BLA to IL during extinction. Finally, the accelerated extinction learning by infusion of exogenous BDNF in the BLA could also be blocked by IL infusion of BDNF-neutralizing antibody rather than vice versa, indicating that the IL, but not BLA, is the primary action site of BDNF in CTA extinction. Together, these data suggest that BLA-IL circuit regulates CTA memory extinction by identifying BDNF as a key regulator.

  13. Extinction-Optimized Volume Illumination.

    Science.gov (United States)

    Ament, Marco; Zirr, Tobias; Dachsbacher, Carsten

    2016-05-16

    We present a novel method to optimize the attenuation of light for the single scattering model in direct volume rendering. A common problem of single scattering is the high dynamic range between lit and shadowed regions due to the exponential attenuation of light along a ray. Moreover, light is often attenuated too strong between a sample point and the camera, hampering the visibility of important features. Our algorithm employs an importance function to selectively illuminate important structures and make them visible from the camera. With the importance function, more light can be transmitted to the features of interest, while contextual structures cast shadows which provide visual cues for perception of depth. At the same time, more scattered light is transmitted from the sample point to the camera to improve the primary visibility of important features. We formulate a minimization problem that automatically determines the extinction along a view or shadow ray to obtain a good balance between sufficient transmittance and attenuation. In contrast to previous approaches, we do not require a computationally expensive solution of a global optimization, but instead provide a closed-form solution for each sampled extinction value along a view or shadow ray and thus achieve interactive performance.

  14. Phylogenetic Clustering of Origination and Extinction across the Late Ordovician Mass Extinction.

    Directory of Open Access Journals (Sweden)

    Andrew Z Krug

    Full Text Available Mass extinctions can have dramatic effects on the trajectory of life, but in some cases the effects can be relatively small even when extinction rates are high. For example, the Late Ordovician mass extinction is the second most severe in terms of the proportion of genera eliminated, yet is noted for the lack of ecological consequences and shifts in clade dominance. By comparison, the end-Cretaceous mass extinction was less severe but eliminated several major clades while some rare surviving clades diversified in the Paleogene. This disconnect may be better understood by incorporating the phylogenetic relatedness of taxa into studies of mass extinctions, as the factors driving extinction and recovery are thought to be phylogenetically conserved and should therefore promote both origination and extinction of closely related taxa. Here, we test whether there was phylogenetic selectivity in extinction and origination using brachiopod genera from the Middle Ordovician through the Devonian. Using an index of taxonomic clustering (RCL as a proxy for phylogenetic clustering, we find that A both extinctions and originations shift from taxonomically random or weakly clustered within families in the Ordovician to strongly clustered in the Silurian and Devonian, beginning with the recovery following the Late Ordovician mass extinction, and B the Late Ordovician mass extinction was itself only weakly clustered. Both results stand in stark contrast to Cretaceous-Cenozoic bivalves, which showed significant levels of taxonomic clustering of extinctions in the Cretaceous, including strong clustering in the mass extinction, but taxonomically random extinctions in the Cenozoic. The contrasting patterns between the Late Ordovician and end-Cretaceous events suggest a complex relationship between the phylogenetic selectivity of mass extinctions and the long-term phylogenetic signal in origination and extinction patterns.

  15. Selectivity of terrestrial gastropod extinctions on an oceanic archipelago and insights into the anthropogenic extinction process

    OpenAIRE

    Chiba, Satoshi; Roy, Kaustuv

    2011-01-01

    Anthropogenic impacts have led to widespread extinctions of species on oceanic islands but the nature of many of these extinctions remains poorly known. Here we investigate extinction selectivities of terrestrial gastropods from the Ogasawara archipelago in the northwest Pacific, where anthropogenic threats have changed over time, shifting primarily from the effects of habitat loss to predation by a variety of different predators. Across all of the islands, extinct species had significantly s...

  16. Opioid receptors in the midbrain periaqueductal gray regulate extinction of pavlovian fear conditioning.

    Science.gov (United States)

    McNally, Gavan P; Pigg, Michael; Weidemann, Gabrielle

    2004-08-01

    Four experiments studied the role of opioid receptors in the midbrain periaqueductal gray matter (PAG), an important structure eliciting conditioned fear responses, in the extinction of Pavlovian fear. Rats received pairings of an auditory conditioned stimulus (CS) with a foot shock unconditioned stimulus (US). The freezing conditioned response (CR) elicited by the CS was then extinguished via nonreinforced presentations of the CS. Microinjection of the opioid receptor antagonist naloxone into the ventrolateral PAG (vlPAG) before nonrein-forced CS presentations impaired development of extinction, but such microinjections at the end of extinction did not reinstate an already extinguished freezing CR. This role for opioid receptors in fear extinction was specific to the vlPAG because infusions of naloxone into the dorsal PAG did not impair fear extinction. Finally, the impairment of fear extinction produced by vlPAG infusions of naloxone was dose-dependent. These results show for the first time that the midbrain PAG contributes to fear extinction and specifically identify a role for vlPAG opioid receptors in the acquisition but not the expression of such extinction. Taken together with our previous findings, we suggest that, during fear conditioning, activation of vlPAG opioid receptors contributes to detection of the discrepancy between the actual and expected outcome of the conditioning trial. vlPAG opioid receptors regulate the learning that accrues to the CS and other stimuli present on a trial because they instantiate an associative error correction process influencing US information reaching the site of CS-US convergence in the amygdala. During nonreinforcement, this vlPAG opioid receptor contribution signals extinction.

  17. The influence of partner cues on the extinction of causal judgments in people.

    Science.gov (United States)

    Holmes, Nathan M; Griffiths, Oren; Westbrook, R Frederick

    2014-09-01

    Studies in laboratory animals have shown that the extinction of a conditioned stimulus, A, is regulated by the associative history of a second stimulus, X, when the two are extinguished in simultaneous compound: An inhibitory X protects A from extinction (Rescorla Learning & Behavior, 31, 124-132, 2003), whereas an excitatory X facilitates, and under some circumstances deepens, the extinction of A (Rescorla Journal of Experimental Psychology: Animal Behavior Processes, 26, 251-260, 2000, Journal of Experimental Psychology: Animal Behavior Processes, 32, 135-144, 2006). In the present study, we used the allergist task to examine whether the extinction of causal judgments in people is similarly regulated by the causal status of co-present stimuli. Experiment 1 showed that a cue trained as a conditioned inhibitor protected a target cue from extinction: The target extinguished in compound with the inhibitor was rated as being more causal of the outcome than was a target extinguished in compound with a control cue lacking inhibitory properties. In contrast, the remaining experiments showed that the extinction of a target cue was regulated by the presence, but not the causal status, of a partner cue: Target cues extinguished in compound were protected from extinction, and no evidence showed that an already extinguished partner conferred more protection (Exp. 2), or that an excitatory partner conferred any less protection (Exps. 2 and 3), or that an excitatory partner deepened the extinction of its already extinguished target. These findings are inconsistent with elemental models that rely on a common error term to explain associative changes in extinction. They are largely, but not completely, consistent with the configural model proposed by Pearce (Psychological Review, 94, 61-73, 1987), which predicts an ordering of levels of protection that was not observed.

  18. Timing of extinction relative to acquisition: A parametric analysis of fear extinction in humans

    NARCIS (Netherlands)

    Norrholm, S.D.; Vervliet, B.; Jovanovic, T.; Boshoven, W.; Myers, K.M.; Davis, M.; Rothbaum, B.O.; Duncan, E.J.

    2008-01-01

    Fear extinction is a reduction in conditioned fear following repeated exposure to the feared cue in the absence of any aversive event. Extinguished fear often reappears after extinction through spontaneous recovery. Animal studies suggest that spontaneous recovery can be abolished if extinction occu

  19. Constraints on Enhanced Extinction Resulting from Extinction Treatment in the Presence of an Added Excitor

    Science.gov (United States)

    Urcelay, Gonzalo P.; Lipatova, Olga; Miller, Ralph R.

    2009-01-01

    Three Pavlovian fear conditioning experiments with rats as subjects explored the effect of extinction in the presence of a concurrent excitor. Our aim was to explore this particular treatment, documented in previous studies to deepen extinction, with novel control groups to shed light on the processes involved in extinction. Relative to subjects…

  20. Mass Extinction And The Structure Of The Milky Way

    CERN Document Server

    Filipović, M D; Crawford, E J; Tothill, N F H

    2013-01-01

    We use the most up to date Milky Way model and solar orbit data in order to test the hypothesis that the Sun's galactic spiral arm crossings cause mass extinction events on Earth. To do this, we created a new model of the Milky Way's spiral arms by combining a large quantity of data from several surveys. We then combined this model with a recently derived solution for the solar orbit to determine the timing of the Sun's historical passages through the Galaxy's spiral arms. Our new model was designed with a symmetrical appearance, with the major alteration being the addition of a spur at the far side of the Galaxy. A correlation was found between the times at which the Sun crosses the spiral arms and six known mass extinction events. Furthermore, we identify five additional historical mass extinction events that might be explained by the motion of the Sun around our Galaxy. These five additional significant drops in marine genera that we find include significant reductions in diversity at 415, 322, 300, 145 an...

  1. Mass extinction and the structure of the milky way

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    Filipović M.D.

    2013-01-01

    Full Text Available We use the most up-to-date Milky Way model and solar orbit data in order to test the hypothesis that the Sun's galactic spiral arm crossings cause mass extinction events on Earth. To do this, we created a new model of the Milky Way's spiral arms by combining a large quantity of data from several surveys. We then combined this model with a recently derived solution for the solar orbit to determine the timing of the Sun's historical passages through the Galaxy's spiral arms. Our new model was designed with a symmetrical appearance, with the major alteration being the addition of a spur at the far side of the Galaxy. A correlation was found between the times at which the Sun crosses the spiral arms and six known mass extinction events. Furthermore, we identify five additional historical mass extinction events that might be explained by the motion of the Sun around our Galaxy. These five additional significant drops in marine genera that we find include significant reductions in diversity at 415, 322, 300, 145 and 33 Myr ago. Our simulations indicate that the Sun has spent ~60% of its time passing through our Galaxy's various spiral arms. Also, we briefly discuss and combine previous work on the Galactic Habitable Zone with the new Milky Way model.

  2. Towards mouse models of perseveration: a heritable component in extinction of operant behavior in fourteen standard and recombinant inbred mouse lines.

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    Malkki, Hemi A I; Donga, Laura A B; de Groot, Sabine E; Battaglia, Francesco P; Pennartz, Cyriel M A

    2011-09-01

    Extinction of instrumental responses is an essential skill for adaptive behavior such as foraging. So far, only few studies have focused on extinction following appetitive conditioning in mice. We studied extinction of appetitive operant lever-press behavior in six standard inbred mouse strains (A/J, C3H/HeJ, C57BL/6J, DBA/2J, BALB/cByJ and NOD/Ltj) and eight recombinant inbred mouse lines. From the response rates at the end of operant and extinction training we computed an extinction index, with higher values indicating better capability to omit behavioral responding in absence of reward. This index varied highly across the mouse lines tested, and the variability was partially due to a significant heritable component of 12.6%. To further characterize the relationship between operant learning and extinction, we calculated the slope of the time course of extinction across sessions. While many strains showed a considerable capacity to omit responding when lever pressing was no longer rewarded, we found a few lines showing an abnormally high perseveration in lever press behavior, showing no decay in response scores over extinction sessions. No correlation was found between operant and extinction response scores, suggesting that appetitive operant learning and extinction learning are dissociable, a finding in line with previous studies indicating that these forms of learning are dependent on different brain areas. These data shed light on the heritable basis of extinction learning and may help develop animal models of addictive habits and other perseverative disorders, such as compulsive food seeking and eating.

  3. Comparing counterconditioning and extinction as methods to reduce fear of movement-related pain

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    Meulders, A.; Karsdorp, P.A.; Claes, N.; Vlaeyen, J.W.S.

    2015-01-01

    Cognitive-behavioral treatments for chronic pain typically target pain-related fear; exposure in vivo is a common treatment focusing on disconfirming harm expectancy of feared movements. Exposure therapy is tailored on Pavlovian extinction; an alternative fear reduction technique that also alters st

  4. Orexin/hypocretin receptor 1 signaling mediates Pavlovian cue-food conditioning and extinction.

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    Keefer, Sara E; Cole, Sindy; Petrovich, Gorica D

    2016-08-01

    Learned food cues can drive feeding in the absence of hunger, and orexin/hypocretin signaling is necessary for this type of overeating. The current study examined whether orexin also mediates cue-food learning during the acquisition and extinction of these associations. In Experiment 1, rats underwent two sessions of Pavlovian appetitive conditioning, consisting of tone-food presentations. Prior to each session, rats received either the orexin 1 receptor antagonist SB-334867 (SB) or vehicle systemically. SB treatment did not affect conditioned responses during the first conditioning session, measured as food cup behavior during the tone and latency to approach the food cup after the tone onset, compared to the vehicle group. During the second conditioning session, SB treatment attenuated learning. All groups that received SB, prior to either the first or second conditioning session, displayed significantly less food cup behavior and had longer latencies to approach the food cup after tone onset compared to the vehicle group. These findings suggest orexin signaling at the 1 receptor mediates the consolidation and recall of cue-food acquisition. In Experiment 2, another group of rats underwent tone-food conditioning sessions (drug free), followed by two extinction sessions under either SB or vehicle treatment. Similar to Experiment 1, SB did not affect conditioned responses during the first session. During the second extinction session, the group that received SB prior to the first extinction session, but vehicle prior to the second, expressed conditioned food cup responses longer after tone offset, when the pellets were previously delivered during conditioning, and maintained shorter latencies to approach the food cup compared to the other groups. The persistence of these conditioned behaviors indicates impairment in extinction consolidation due to SB treatment during the first extinction session. Together, these results demonstrate an important role for orexin

  5. A NMDA receptor antagonist, MK-801 impairs consolidating extinction of auditory conditioned fear responses in a Pavlovian model.

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    Jun-Li Liu

    Full Text Available BACKGROUND: In auditory fear conditioning, repeated presentation of the tone in the absence of shock leads to extinction of the acquired fear responses. The glutamate N-methyl-D-aspartate receptor (NMDAR is thought to be involved in the extinction of the conditioned fear responses, but its detailed role in initiating and consolidating or maintaining the fear extinction memory is unclear. Here we investigated this issue by using a NMDAR antagonist, MK-801. METHODS/MAIN FINDINGS: The effects of immediate (beginning at 10 min after the conditioning and delayed (beginning at 24 h after conditioning extinctions were first compared with the finding that delayed extinction caused a better and long-lasting (still significant on the 20(th day after extinction depression on the conditioned fear responses. In a second experiment, MK-801 was intraperitoneally (i.p. injected at 40 min before, 4 h or 12 h after the delayed extinction, corresponding to critical time points for initiating, consolidating or maintaining the fear extinction memory. i.p. injection of MK-801 at either 40 min before or 4 h after delayed extinction resulted in an impairment of initiating and consolidating fear extinction memory, which caused a long lasting increased freezing score that was still significant on the 7th day after extinction, compared with extinction group. However, MK-801 administered at 12 h after the delayed extinction, when robust consolidation has been occurred and stabilized, did not affect the established extinction memory. Furthermore, the changed freezing behaviors was not due to an alteration in general anxiety levels, since MK-801 treatment had no effect on the percentage of open-arm time or open-arm entries in an Elevated Plus Maze (EPM task. CONCLUSIONS/SIGNIFICANCE: Our data suggested that the activation of NMDARs plays important role in initiation and consolidation but not maintenance of fear extinction memory. Together with the fact that NMDA receptor is

  6. Reinforcer devaluation by extinction depends on the food restriction protocol.

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    Baker, Tyson W; Weisman, Ronald G; Beninger, Richard J

    2012-05-01

    A common feature of reinforcer devaluation studies is that new learning induces the devaluation. The present study used extinction to induce new learning about the conditioned reinforcer in a heterogeneous chain schedule. Rats pressed a lever in a heterogeneous chain schedule to produce a conditioned reinforcer (light) associated with the opportunity to obtain an unconditioned reinforcer (food) by pulling a chain. The density of food reinforcement correlated with the conditioned reinforcer was varied in a comparison of continuous and variable-ratio reinforcement schedules of chain pulling; this had no noticeable effect on conditioned reinforcer devaluation produced by extinction of chain pulling. In contrast, how rats were deprived appeared to matter very much. Restricting meal duration to 1h daily produced more lever pressing during baseline training and a greater reductive effect of devaluation on lever pressing than restricting body weight to 80% of a control rat's weight, which eliminated the devaluation effect. Further analysis suggested that meal-duration restriction may have produced devaluation effects because it was more effective than weight restriction in reducing rats' body weights. Our results exposed an important limitation on the devaluation of conditioned reinforcers: slight differences in food restriction, using two commonly employed food-restriction procedures, can produce completely different interpretations of reinforcer devaluation while leaving reinforcer-based learning intact.

  7. An allometric approach to quantify the extinction vulnerability of birds and mammals.

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    Hilbers, J P; Schipper, A M; Hendriks, A J; Verones, F; Pereira, H M; Huijbregts, M A J

    2016-03-01

    -specific information. The framework facilitates the estimation of extinction vulnerabilities of data-deficient species. It may be applied to forecast extinction vulnerability in response to a changing environment, by incorporating quantitative relationships between wildlife demographic parameters and environmental drivers like habitat alteration, climate change, or hunting.

  8. Long-Term Maintenance of Immediate or Delayed Extinction Is Determined by the Extinction-Test Interval

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    Johnson, Justin S.; Escobar, Martha; Kimble, Whitney L.

    2010-01-01

    Short acquisition-extinction intervals (immediate extinction) can lead to either more or less spontaneous recovery than long acquisition-extinction intervals (delayed extinction). Using rat subjects, we observed less spontaneous recovery following immediate than delayed extinction (Experiment 1). However, this was the case only if a relatively…

  9. The Role of the Medial Prefrontal Cortex-Amygdala Circuit in Stress Effects on the Extinction of Fear

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    Irit Akirav

    2007-01-01

    Full Text Available Stress exposure, depending on its intensity and duration, affects cognition and learning in an adaptive or maladaptive manner. Studies addressing the effects of stress on cognitive processes have mainly focused on conditioned fear, since it is suggested that fear-motivated learning lies at the root of affective and anxiety disorders. Inhibition of fear-motivated response can be accomplished by experimental extinction of the fearful response to the fear-inducing stimulus. Converging evidence indicates that extinction of fear memory requires plasticity in both the medial prefrontal cortex and the amygdala. These brain areas are also deeply involved in mediating the effects of exposure to stress on memory. Moreover, extensive evidence indicates that gamma-aminobutyric acid (GABA transmission plays a primary role in the modulation of behavioral sequelae resulting from a stressful experience, and may also partially mediate inhibitory learning during extinction. In this review, we present evidence that exposure to a stressful experience may impair fear extinction and the possible involvement of the GABA system. Impairment of fear extinction learning is particularly important as it may predispose some individuals to the development of posttraumatic stress disorder. We further discuss a possible dysfunction in the medial prefrontal cortex-amygdala circuit following a stressful experience that may explain the impaired extinction caused by exposure to a stressor.

  10. Seed dispersal anachronisms: rethinking the fruits extinct megafauna ate.

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    Paulo R Guimarães

    Full Text Available BACKGROUND: Some neotropical, fleshy-fruited plants have fruits structurally similar to paleotropical fruits dispersed by megafauna (mammals > 10(3 kg, yet these dispersers were extinct in South America 10-15 Kyr BP. Anachronic dispersal systems are best explained by interactions with extinct animals and show impaired dispersal resulting in altered seed dispersal dynamics. METHODOLOGY/PRINCIPAL FINDINGS: We introduce an operational definition of megafaunal fruits and perform a comparative analysis of 103 Neotropical fruit species fitting this dispersal mode. We define two megafaunal fruit types based on previous analyses of elephant fruits: fruits 4-10 cm in diameter with up to five large seeds, and fruits > 10 cm diameter with numerous small seeds. Megafaunal fruits are well represented in unrelated families such as Sapotaceae, Fabaceae, Solanaceae, Apocynaceae, Malvaceae, Caryocaraceae, and Arecaceae and combine an overbuilt design (large fruit mass and size with either a single or few ( 100 seeds. Within-family and within-genus contrasts between megafaunal and non-megafaunal groups of species indicate a marked difference in fruit diameter and fruit mass but less so for individual seed mass, with a significant trend for megafaunal fruits to have larger seeds and seediness. CONCLUSIONS/SIGNIFICANCE: Megafaunal fruits allow plants to circumvent the trade-off between seed size and dispersal by relying on frugivores able to disperse enormous seed loads over long-distances. Present-day seed dispersal by scatter-hoarding rodents, introduced livestock, runoff, flooding, gravity, and human-mediated dispersal allowed survival of megafauna-dependent fruit species after extinction of the major seed dispersers. Megafauna extinction had several potential consequences, such as a scale shift reducing the seed dispersal distances, increasingly clumped spatial patterns, reduced geographic ranges and limited genetic variation and increased among

  11. Can Parallelingualism Save Norwegian from Extinction?

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    Linn, Andrew R.

    2010-01-01

    Language extinction is one of the most pressing issues in linguistics today, and the literature is full of discussion about how to combat it. Statements that Norwegian is amongst the languages that are already extinct are merely examples of a widespread tendency in the literature towards erroneous information about Norwegian. Nonetheless, there is…

  12. Periodicity of extinction: A 1988 update

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    Sepkowski, J. John, Jr.

    1988-01-01

    The hypothesis that events of mass extinction recur periodically at approximately 26 my intervals is an empirical claim based on analysis of data from the fossil record. The hypothesis has become closely linked with catastrophism because several events in the periodic series are associated with evidence of extraterrestrial impacts, and terrestrial forcing mechanisms with long, periodic recurrences are not easily conceived. Astronomical mechanisms that have been hypothesized include undetected solar companions and solar oscillation about the galactic plane, which induce comet showers and result in impacts on Earth at regular intervals. Because these mechanisms are speculative, they have been the subject of considerable controversy, as has the hypothesis of periodicity of extinction. In response to criticisms and uncertainties, a data base was developed on times of extinction of marine animal genera. A time series is given and analyzed with 49 sample points for the per-genus extinction rate from the Late Permian to the Recent. An unexpected pattern in the data is the uniformity of magnitude of many of the periodic extinction events. Observations suggest that the sequence of extinction events might be the result of two sets of mechanisms: a periodic forcing that normally induces only moderate amounts of extinction, and independent incidents or catastrophes that, when coincident with the periodic forcing, amplify its signal and produce major-mass extinctions.

  13. Extinction-Induced Variability in Human Behavior

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    Kinloch, Jennifer M.; Foster, T. Mary; McEwan, James S. A.

    2009-01-01

    Participants earned points by pressing a computer space bar (Experiment 1) or forming rectangles on the screen with the mouse (Experiment 2) under differential-reinforcement-of-low-rate schedules, followed by extinction. Variability in interresponse time (the contingent dimension) increased during extinction, as for Morgan and Lee (1996);…

  14. Current extinction rates of reptiles and amphibians.

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    Alroy, John

    2015-10-20

    There is broad concern that a mass extinction of amphibians and reptiles is now underway. Here I apply an extremely conservative Bayesian method to estimate the number of recent amphibian and squamate extinctions in nine important tropical and subtropical regions. The data stem from a combination of museum collection databases and published site surveys. The method computes an extinction probability for each species by considering its sighting frequency and last sighting date. It infers hardly any extinction when collection dates are randomized and it provides underestimates when artificial extinction events are imposed. The method also appears to be insensitive to trends in sampling; therefore, the counts it provides are absolute minimums. Extinctions or severe population crashes have accumulated steadily since the 1970s and 1980s, and at least 3.1% of frog species have already disappeared. Based on these data and this conservative method, the best estimate of the global grand total is roughly 200 extinctions. Consistent with previous results, frog losses are heavy in Latin America, which has been greatly affected by the pathogenic chytrid fungus Batrachochytrium dendrobatidis. Extinction rates are now four orders-of-magnitude higher than background, and at least another 6.9% of all frog species may be lost within the next century, even if there is no acceleration in the growth of environmental threats.

  15. The contextual brain: implications for fear conditioning, extinction and psychopathology

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    Maren, Stephen; Phan, K. Luan; Liberzon, Israel

    2016-01-01

    Contexts surround and imbue meaning to events; they are essential for recollecting the past, interpreting the present and anticipating the future. Indeed, the brain’s capacity to contextualize information permits enormous cognitive and behavioural flexibility. Studies of Pavlovian fear conditioning and extinction in rodents and humans suggest that a neural circuit including the hippocampus, amygdala and medial prefrontal cortex is involved in the learning and memory processes that enable context-dependent behaviour. Dysfunction in this network may be involved in several forms of psychopathology, including post-traumatic stress disorder, schizophrenia and substance abuse disorders. PMID:23635870

  16. Deep-time phylogenetic clustering of extinctions in an evolutionarily dynamic clade (Early Jurassic ammonites.

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    Clotilde Hardy

    Full Text Available Conservation biologists and palaeontologists are increasingly investigating the phylogenetic distribution of extinctions and its evolutionary consequences. However, the dearth of palaeontological studies on that subject and the lack of methodological consensus hamper our understanding of that major evolutionary phenomenon. Here we address this issue by (i reviewing the approaches used to quantify the phylogenetic selectivity of extinctions and extinction risks; (ii investigating with a high-resolution dataset whether extinctions and survivals were phylogenetically clustered among early Pliensbachian (Early Jurassic ammonites; (iii exploring the phylogenetic and temporal maintenance of this signal. We found that ammonite extinctions were significantly clumped phylogenetically, a pattern that prevailed throughout the 6.6 Myr-long early Pliensbachian interval. Such a phylogenetic conservatism did not alter--or may even have promoted--the evolutionary success of this major cephalopod clade. However, the comparison of phylogenetic autocorrelation among studies remains problematic because the notion of phylogenetic conservatism is scale-dependent and the intensity of the signal is sensitive to temporal resolution. We recommend a combined use of Moran's I, Pearson's ϕ and Fritz and Purvis' D statistics because they highlight different facets of the phylogenetic pattern of extinctions and/or survivals.

  17. Mass extinction in poorly known taxa.

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    Régnier, Claire; Achaz, Guillaume; Lambert, Amaury; Cowie, Robert H; Bouchet, Philippe; Fontaine, Benoît

    2015-06-23

    Since the 1980s, many have suggested we are in the midst of a massive extinction crisis, yet only 799 (0.04%) of the 1.9 million known recent species are recorded as extinct, questioning the reality of the crisis. This low figure is due to the fact that the status of very few invertebrates, which represent the bulk of biodiversity, have been evaluated. Here we show, based on extrapolation from a random sample of land snail species via two independent approaches, that we may already have lost 7% (130,000 extinctions) of the species on Earth. However, this loss is masked by the emphasis on terrestrial vertebrates, the target of most conservation actions. Projections of species extinction rates are controversial because invertebrates are essentially excluded from these scenarios. Invertebrates can and must be assessed if we are to obtain a more realistic picture of the sixth extinction crisis.

  18. Synchronous extinction of North America's Pleistocene mammals

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    Faith, J. Tyler; Surovell, Todd A.

    2009-12-01

    The late Pleistocene witnessed the extinction of 35 genera of North American mammals. The last appearance dates of 16 of these genera securely fall between 12,000 and 10,000 radiocarbon years ago (≈13,800-11,400 calendar years B.P.), although whether the absence of fossil occurrences for the remaining 19 genera from this time interval is the result of sampling error or temporally staggered extinctions is unclear. Analysis of the chronology of extinctions suggests that sampling error can explain the absence of terminal Pleistocene last appearance dates for the remaining 19 genera. The extinction chronology of North American Pleistocene mammals therefore can be characterized as a synchronous event that took place 12,000-10,000 radiocarbon years B.P. Results favor an extinction mechanism that is capable of wiping out up to 35 genera across a continent in a geologic instant.

  19. Adolescent traumatic stress experience results in less robust conditioned fear and post-extinction fear cue responses in adult rats.

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    Moore, Nicole L T; Gauchan, Sangeeta; Genovese, Raymond F

    2014-05-01

    Early exposure to a traumatic event may produce lasting effects throughout the lifespan. Traumatic stress during adolescence may deliver a distinct developmental insult compared with more-often studied neonatal or juvenile traumatic stress paradigms. The present study describes the lasting effects of adolescent traumatic stress upon adulthood fear conditioning. Adolescent rats were exposed to a traumatic stressor (underwater trauma, UWT), then underwent fear conditioning during adulthood. Fear extinction was tested over five conditioned suppression extinction sessions three weeks later. The efficacies of two potential extinction-enhancing compounds, endocannabinoid reuptake inhibitor AM404 (10mg/kg) and M1 muscarinic positive allosteric modulator BQCA (10mg/kg), were also assessed. Finally, post-extinction fear responses were examined using a fear cue (light) as a prepulse stimulus. Rats traumatically stressed during adolescence showed blunted conditioned suppression on day 1 of extinction training, and AM404 reversed this effect. Post-extinction startle testing showed that fear conditioning eliminates prepulse inhibition to the light cue. Startle potentiation was observed only in rats without adolescent UWT exposure. AM404 and BQCA both ameliorated this startle potentiation, while BQCA increased startle in the UWT group. These results suggest that exposure to a traumatic stressor during adolescence alters developmental outcomes related to stress response and fear extinction compared to rats without adolescent traumatic stress exposure, blunting the adulthood fear response and reducing residual post-extinction fear expression. Efficacy of pharmacological interventions may also vary as a factor of developmental traumatic stress exposure.

  20. Adolescent alcohol exposure reduces behavioral flexibility, promotes disinhibition, and increases resistance to extinction of ethanol self-administration in adulthood.

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    Gass, Justin T; Glen, William Bailey; McGonigal, Justin T; Trantham-Davidson, Heather; Lopez, Marcelo F; Randall, Patrick K; Yaxley, Richard; Floresco, Stan B; Chandler, L Judson

    2014-10-01

    The prefrontal cortex (PFC) is a brain region that is critically involved in cognitive function and inhibitory control of behavior, and adolescence represents an important period of continued PFC development that parallels the maturation of these functions. Evidence suggests that this period of continued development of the PFC may render it especially vulnerable to environmental insults that impact PFC function in adulthood. Experimentation with alcohol typically begins during adolescence when binge-like consumption of large quantities is common. In the present study, we investigated the effects of repeated cycles of adolescent intermittent ethanol (AIE) exposure (postnatal days 28-42) by vapor inhalation on different aspects of executive functioning in the adult rat. In an operant set-shifting task, AIE-exposed rats exhibited deficits in their ability to shift their response strategy when the rules of the task changed, indicating reduced behavioral flexibility. There were no differences in progressive ratio response for the reinforcer suggesting that AIE did not alter reinforcer motivation. Examination of performance on the elevated plus maze under conditions designed to minimize stress revealed that AIE exposure enhanced the number of entries into the open arms, which may reflect either reduced anxiety and/or disinhibition of exploratory-like behavior. In rats that trained to self-administer ethanol in an operant paradigm, AIE increased resistance to extinction of ethanol-seeking behavior. This resistance to extinction was reversed by positive allosteric modulation of mGluR5 during extinction training, an effect that is thought to reflect promotion of extinction learning mechanisms within the medial PFC. Consistent with this, CDPPB was also observed to reverse the deficits in behavioral flexibility. Finally, diffusion tensor imaging with multivariate analysis of 32 brain areas revealed that while there were no differences in the total brain volume, the volume of

  1. Human fear conditioning and extinction in neuroimaging: a systematic review.

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    Christina Sehlmeyer

    Full Text Available Fear conditioning and extinction are basic forms of associative learning that have gained considerable clinical relevance in enhancing our understanding of anxiety disorders and facilitating their treatment. Modern neuroimaging techniques have significantly aided the identification of anatomical structures and networks involved in fear conditioning. On closer inspection, there is considerable variation in methodology and results between studies. This systematic review provides an overview of the current neuroimaging literature on fear conditioning and extinction on healthy subjects, taking into account methodological issues such as the conditioning paradigm. A Pubmed search, as of December 2008, was performed and supplemented by manual searches of bibliographies of key articles. Two independent reviewers made the final study selection and data extraction. A total of 46 studies on cued fear conditioning and/or extinction on healthy volunteers using positron emission tomography or functional magnetic resonance imaging were reviewed. The influence of specific experimental factors, such as contingency and timing parameters, assessment of conditioned responses, and characteristics of conditioned and unconditioned stimuli, on cerebral activation patterns was examined. Results were summarized descriptively. A network consisting of fear-related brain areas, such as amygdala, insula, and anterior cingulate cortex, is activated independently of design parameters. However, some neuroimaging studies do not report these findings in the presence of methodological heterogeneities. Furthermore, other brain areas are differentially activated, depending on specific design parameters. These include stronger hippocampal activation in trace conditioning and tactile stimulation. Furthermore, tactile unconditioned stimuli enhance activation of pain related, motor, and somatosensory areas. Differences concerning experimental factors may partly explain the variance

  2. The Histone Deacetylase Inhibitor Valproic Acid Enhances Acquisition, Extinction, and Reconsolidation of Conditioned Fear

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    Bredy, Timothy W.; Barad, Mark

    2008-01-01

    Histone modifications contribute to the epigenetic regulation of gene expression, a process now recognized to be important for the consolidation of long-term memory. Valproic acid (VPA), used for many years as an anticonvulsant and a mood stabilizer, has effects on learning and memory and enhances the extinction of conditioned fear through its…

  3. A Unifying Model of the Role of the Infralimbic Cortex in Extinction and Habits

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    Barker, Jacqueline M.; Taylor, Jane R.; Chandler, L. Judson

    2014-01-01

    The infralimbic prefrontal cortex (IL) has been shown to be critical for the regulation of flexible behavior, but its precise function remains unclear. This region has been shown to be critical for the acquisition, consolidation, and expression of extinction learning, leading many to hypothesize that IL suppresses behavior as part of a…

  4. Teens that fear screams: A comparison of fear conditioning, extinction, and reinstatement in adolescents and adults.

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    Den, Miriam Liora; Graham, Bronwyn M; Newall, Carol; Richardson, Rick

    2015-11-01

    This study investigated differences between adolescents and adults on fear conditioning, extinction, and reinstatement (i.e., the recovery of conditioned fear following re-exposure to the unconditioned stimulus [US] post-extinction). Participants underwent differential conditioning (i.e., the Screaming Lady) where one neutral face (CS+) was followed by the same face expressing fear and a loud scream (US) while another neutral face (CS-) remained neutral. Extinction involved non-reinforced presentations of both CSs, after which participants were reinstated (2xUSs) or not. On two self-report measures, both ages showed conditioning, good extinction learning and retention, and reinstatement-induced relapse. However, only adolescents showed conditioning, extinction, and reinstatement on the eye tracking measure; relapse on this measure could not be assessed in adults given they did not show initial conditioning. Lastly, higher levels of depression predicted stronger conditioning and weaker extinction in adolescents only. These findings are discussed in terms of their implications for adolescent anxiety disorders.

  5. Auditory Cortex is Important in the Extinction of Two Different Tone-Based Conditioned Fear Memories in Rats.

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    Song, Eun Young; Boatman, Jeffrey A; Jung, Min Whan; Kim, Jeansok J

    2010-01-01

    Extensive fear extinction research is guided by the view that there are structures in the brain that develop inhibitory control over the expression of conditioned fear memories. While the medial prefrontal cortex has recently captured attention as the locus of plasticity essential for extinction of conditioned fear, the auditory cortex is another plausible cortical area involved in extinction learning since it is considered a sufficient conditioned stimulus (CS) pathway in tone fear conditioning. We examined the role of auditory cortex in extinction of auditory-based fear memories with a standard tone-on conditioning, wherein a tone CS predicted a footshock unconditioned stimulus (US), or a novel tone-off conditioning, in which the tone was continually present and the offset of the tone was the CS predicting the US. Rats with bilateral auditory cortex lesions were trained in either paradigm and subsequently trained in extinction to the CS. Auditory cortex lesions had no effect on acquisition but impaired extinction to both CSs. These findings indicate that the auditory cortex contributes to extinction of wide-ranging auditory fear memories, as evidenced by deficits in both tone-on CS and tone-off CS extinction training.

  6. Predicted Shifts in Small Mammal Distributions and Biodiversity in the Altered Future Environment of Alaska: An Open Access Data and Machine Learning Perspective.

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    A P Baltensperger

    Full Text Available Climate change is acting to reallocate biomes, shift the distribution of species, and alter community assemblages in Alaska. Predictions regarding how these changes will affect the biodiversity and interspecific relationships of small mammals are necessary to pro-actively inform conservation planning. We used a set of online occurrence records and machine learning methods to create bioclimatic envelope models for 17 species of small mammals (rodents and shrews across Alaska. Models formed the basis for sets of species-specific distribution maps for 2010 and were projected forward using the IPCC (Intergovernmental Panel on Climate Change A2 scenario to predict distributions of the same species for 2100. We found that distributions of cold-climate, northern, and interior small mammal species experienced large decreases in area while shifting northward, upward in elevation, and inland across the state. In contrast, many southern and continental species expanded throughout Alaska, and also moved down-slope and toward the coast. Statewide community assemblages remained constant for 15 of the 17 species, but distributional shifts resulted in novel species assemblages in several regions. Overall biodiversity patterns were similar for both time frames, but followed general species distribution movement trends. Biodiversity losses occurred in the Yukon-Kuskokwim Delta and Seward Peninsula while the Beaufort Coastal Plain and western Brooks Range experienced modest gains in species richness as distributions shifted to form novel assemblages. Quantitative species distribution and biodiversity change projections should help land managers to develop adaptive strategies for conserving dispersal corridors, small mammal biodiversity, and ecosystem functionality into the future.

  7. Differential involvement of medial prefrontal cortex and basolateral amygdala extracellular signal-regulated kinase in extinction of conditioned taste aversion is dependent on different intervals of extinction following conditioning.

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    Lin, P-Y; Wang, S-P; Tai, M-Y; Tsai, Y-F

    2010-11-24

    Extinction reflects a decrease in the conditioned response (CR) following non-reinforcement of a conditioned stimulus. Behavioral evidence indicates that extinction involves an inhibitory learning mechanism in which the extinguished CR reappears with presentation of an unconditioned stimulus. However, recent studies on fear conditioning suggest that extinction erases the original conditioning if the time interval between fear acquisition and extinction is short. The present study examined the effects of different intervals between acquisition and extinction of the original memory in conditioned taste aversion (CTA). Male Long-Evans rats acquired CTA by associating a 0.2% sucrose solution with malaise induced by i.p. injection of 4 ml/kg 0.15 M LiCl. Two different time intervals, 5 and 24 h, between CTA acquisition and extinction were used. Five or 24 h after CTA acquisition, extinction trials were performed, in which a bottle containing 20 ml of a 0.2% sucrose solution was provided for 10 min without subsequent LiCl injection. If sucrose consumption during the extinction trials was greater than the average water consumption, then rats were considered to have reached CTA extinction. Rats subjected to extinction trials lasting 24 h, but not 5 h, after acquisition re-exhibited the extinguished CR following injection of 0.15 M LiCl alone 7 days after acquisition. Extracellular signal-regulated kinase (ERK) in the medial prefrontal cortex (mPFC) and basolateral nucleus of the amygdala (BLA) was examined by Western blot after the first extinction trial. ERK activation in the mPFC was induced after the extinction trial beginning 5 h after acquisition, whereas the extinction trial performed 24 h after acquisition induced ERK activation in the BLA. These data suggest that the original conditioning can be inhibited or retained by CTA extinction depending on the time interval between acquisition and extinction and that the ERK transduction pathway in the mPFC and BLA is

  8. Avoidant symptoms in PTSD predict fear circuit activation during multimodal fear extinction.

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    Sripada, Rebecca K; Garfinkel, Sarah N; Liberzon, Israel

    2013-01-01

    Convergent evidence suggests that individuals with posttraumatic stress disorder (PTSD) exhibit exaggerated avoidance behaviors as well as abnormalities in Pavlonian fear conditioning. However, the link between the two features of this disorder is not well understood. In order to probe the brain basis of aberrant extinction learning in PTSD, we administered a multimodal classical fear conditioning/extinction paradigm that incorporated affectively relevant information from two sensory channels (visual and tactile) while participants underwent fMRI scanning. The sample consisted of fifteen OEF/OIF veterans with PTSD. In response to conditioned cues and contextual information, greater avoidance symptomatology was associated with greater activation in amygdala, hippocampus, vmPFC, dmPFC, and insula, during both fear acquisition and fear extinction. Heightened responses to previously conditioned stimuli in individuals with more severe PTSD could indicate a deficiency in safety learning, consistent with PTSD symptomatology. The close link between avoidance symptoms and fear circuit activation suggests that this symptom cluster may be a key component of fear extinction deficits in PTSD and/or may be particularly amenable to change through extinction-based therapies.

  9. Resistance to extinction and behavioral momentum.

    Science.gov (United States)

    Nevin, John A

    2012-05-01

    In the metaphor of behavioral momentum, reinforcement is assumed to strengthen discriminated operant behavior in the sense of increasing its resistance to disruption, and extinction is viewed as disruption by contingency termination and reinforcer omission. In multiple schedules of intermittent reinforcement, resistance to extinction is an increasing function of reinforcer rate, consistent with a model based on the momentum metaphor. The partial-reinforcement extinction effect, which opposes the effects of reinforcer rate, can be explained by the large disruptive effect of terminating continuous reinforcement despite its strengthening effect during training. Inclusion of a term for the context of reinforcement during training allows the model to account for a wide range of multiple-schedule extinction data and makes contact with other formulations. The relation between resistance to extinction and reinforcer rate on single schedules of intermittent reinforcement is exactly opposite to that for multiple schedules over the same range of reinforcer rates; however, the momentum model can give an account of resistance to extinction in single as well as multiple schedules. An alternative analysis based on the number of reinforcers omitted to an extinction criterion supports the conclusion that response strength is an increasing function of reinforcer rate during training.

  10. Extinction as discrimination: the molar view.

    Science.gov (United States)

    Baum, William M

    2012-05-01

    The traditional molecular view of behavior explains extinction as the dissipation or inhibition of strength, formerly built up by contiguous reinforcement. In obstinate opposition to this explanation was the partial-reinforcement extinction effect: a partially reinforced response extinguishes more slowly than a continuously reinforced response. It suggests instead that extinction is discrimination. Four pigeons were exposed to daily sessions in which a variable period of food delivery, produced by pecking on a variable-interval schedule, was followed by extinction. The rate of food delivery was varied over a wide range across conditions. Varying the amount of food per delivery inversely with rate of delivery kept response rate from varying excessively. The results confirmed and extended the partial-reinforcement effect; persistence of pecking and time to extinction were inversely related to rate of obtaining food. The results support the molar view of extinction, not as loss of strength of a particular discrete response, but as a transition from one allocation of time among activities to another. Although molecular theories dismiss discrimination due to repeated training and extinction as an impurity or complication, repeated cycles of availability and privation are probably typical of the environment in which most vertebrate species evolved.

  11. Retention of perceptual generalization of fear extinction.

    Science.gov (United States)

    Pappens, Meike; Schroijen, Mathias; Van den Bergh, Omer; Van Diest, Ilse

    2015-12-01

    Fear reduction obtained during a fear extinction procedure can generalize from the extinction stimulus to other perceptually similar stimuli. Perceptual generalization of fear extinction typically follows a perceptual gradient, with increasing levels of fear reduction the more a stimulus resembles the extinction stimulus. The current study aimed to investigate whether perceptual generalization of fear extinction can be observed also after a retention interval of 24h. Fear was acquired to three geometrical figures of different sizes (CS(+), CS1(+) and CS2(+)) by consistently pairing them with a short-lasting suffocation experience (US). Three other geometrical figures that were never followed by the US served as control stimuli (CS(-), CS1(-), CS2(-)). Next, only the CS(+) was extinguished by presenting it in the absence of the US. One day later, fear responses to all stimuli were assessed without any US-presentation. Outcome measures included startle blink EMG, skin conductance, US expectancy, respiratory rate and tidal volume. On day 2 spontaneous recovery of fear was observed in US expectancy and tidal volume, but not in the other outcomes. Evidence for the retention of fear extinction generalization was present in US expectancy and skin conductance, but a perceptual gradient in the retention of generalized fear extinction could not be observed.

  12. Effect of continuous and partial reinforcement on the acquisition and extinction of human conditioned fear.

    Science.gov (United States)

    Grady, Ashley K; Bowen, Kenton H; Hyde, Andrew T; Totsch, Stacie K; Knight, David C

    2016-02-01

    Extinction of Pavlovian conditioned fear in humans is a popular paradigm often used to study learning and memory processes that mediate anxiety-related disorders. Fear extinction studies often only pair the conditioned stimulus (CS) and unconditioned stimulus (UCS) on a subset of acquisition trials (i.e., partial reinforcement/pairing) to prolong extinction (i.e., partial reinforcement extinction effect; PREE) and provide more time to study the process. However, there is limited evidence that the partial pairing procedures typically used during fear conditioning actually extend the extinction process, while there is strong evidence these procedures weaken conditioned response (CR) acquisition. Therefore, determining conditioning procedures that support strong CR acquisition and that also prolong the extinction process would benefit the field. The present study investigated 4 separate CS-UCS pairing procedures to determine methods that support strong conditioning and that also exhibit a PREE. One group (C-C) of participants received continuous CS-UCS pairings; a second group (C-P) received continuous followed by partial CS-UCS pairings; a third group (P-C) received partial followed by continuous CS-UCS pairings; and a fourth group (P-P) received partial CS-UCS pairings during acquisition. A strong skin conductance CR was expressed by C-C and P-C groups but not by C-P and P-P groups at the end of the acquisition phase. The P-C group maintained the CR during extinction. In contrast, the CR extinguished quickly within the C-C group. These findings suggest that partial followed by continuous CS-UCS pairings elicit strong CRs and prolong the extinction process following human fear conditioning.

  13. Inhibition of spontaneous recovery of fear by mGluR5 after prolonged extinction training.

    Directory of Open Access Journals (Sweden)

    Sheng-Chun Mao

    Full Text Available Fear behavior is vital for survival and involves learning contingent associations of non-threatening cues with aversive stimuli. In contrast, excessive levels of fear can be maladaptive and lead to anxiety disorders. Generally, extensive sessions of extinction training correlates with reduced spontaneous recovery. The molecular mechanisms underlying the long-term inhibition of fear recovery following repeated extinction training are not fully understood. Here we show that in rats, prolonged extinction training causes greater reduction in both fear-potentiated startle and spontaneous recovery. This effect was specifically blocked by metabotropic glutamate receptor 5 (mGluR5, but not by mGluR1 antagonists and by a protein synthesis inhibitor. Similar inhibition of memory recovery following prolonged extinction training was also observed in mice. In agreement with the instrumental role of mGluR5 in the prolonged inhibition of fear recovery, we found that FMR1-/- mice which exhibit enhanced mGluR5-mediated signaling exhibit lower spontaneous recovery of fear after extinction training than wild-type littermates. At the molecular level, we discovered that prolonged extinction training reversed the fear conditioning-induced increase in surface expression of GluR1, AMPA/NMDA ratio, postsynaptic density-95 (PSD-95 and synapse-associated protein-97 (SAP97. Accordingly, delivery of Tat-GluR2(3Y, a synthetic peptide that blocks AMPA receptor endocytosis, inhibited prolonged extinction training-induced inhibition of fear recovery. Together, our results demonstrate that prolonged extinction training results in the mGluR5-dependent long-term inhibition of fear recovery. This effect may involve the degradation of original memory and may explain the beneficial effects of prolonged exposure therapy for the treatment of phobias.

  14. A model for evolution and extinction

    CERN Document Server

    Roberts, B W; Roberts, Bruce W

    1995-01-01

    We present a model for evolution and extinction in large ecosystems. The model incorporates the effects of interactions between species and the influences of abiotic environmental factors. We study the properties of the model by approximate analytic solution and also by numerical simulation, and use it to make predictions about the distribution of extinctions and species lifetimes that we would expect to see in real ecosystems. It should be possible to test these predictions against the fossil record. The model indicates that a possible mechanism for mass extinction is the coincidence of a large coevolutionary avalanche in the ecosystem with a severe environmental disturbance.

  15. Volcanogenic Dark Matter and Mass Extinctions

    CERN Document Server

    Abbas, S; Abbas, Samar; Abbas, Afsar

    1996-01-01

    The passage of the Earth through dense clumps of dark matter, the presence of which are predicted by certain cosmologies, would produce large quantities of heat in the interior of this planet through the capture and subsequent annihilation of dark matter particles. This heat can cause large-scale volcanism which could in turn have caused the extinction of the dinosaurs and other mass extinctions. The periodicity of such volcanic outbursts agrees with the frequency of palaeontological mass extinctions as well as the observed periodicity in the occurrence of the largest flood basalt provinces on the globe.

  16. Interstellar extinction by fractal polycrystalline graphite clusters?

    CERN Document Server

    Andersen, A C; Pustovit, V N; Niklasson, G A

    2001-01-01

    Certain dust particles in space are expected to appear as clusters of individual grains. The morphology of these clusters could be fractal or compact. To determine how these structural features would affect the interpretation of the observed interstellar extinction peak at $\\sim 4.6~\\mu$m, we have calculated the extinction by compact and fractal polycrystalline graphite clusters consisting of touching identical spheres. We compare three general methods for computing the extinction of the clusters, namely, a rigorous solution and two different discrete-dipole approximation methods.

  17. A mathematical model for Neanderthal extinction

    CERN Document Server

    Flores, J C

    1997-01-01

    A simple mathematical homogeneous model of competition is used to describe Neanderthal extinction in Europe. It considers two interacting species, Neanderthals and Early Modern Men, in the same ecological niche. Using paleontological data we claim that the parameter of similarity, between both species, fluctuates between 0.992 and 0.997. An extension of the model including migration (diffusion) is also discussed nevertheless, extinction of Neanderthal seems unavoidable. Numerical analysis of travelling wave solution (fronts) comfirms the extinction. The wave-front-velocity is estimated from linear analysis and numerical simulations confirm this estimation. We conjecture a mathematical formulation for the principle of exclusion between competitive interacting species (Gause).

  18. Activation of D1/5 Dopamine Receptors: A Common Mechanism for Enhancing Extinction of Fear and Reward-Seeking Behaviors.

    Science.gov (United States)

    Abraham, Antony D; Neve, Kim A; Lattal, K Matthew

    2016-07-01

    Dopamine is critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine's function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in appetitive tasks. A parallel and growing literature indicates that dopamine signaling is involved in consolidation of memories into stable representations in aversive tasks such as fear conditioning. Relatively little is known about how dopamine may modulate memories that form during extinction, when organisms learn that the relation between previously associated events is severed. We investigated whether fear and reward extinction share common mechanisms that could be enhanced with dopamine D1/5 receptor activation. Pharmacological activation of dopamine D1/5 receptors (with SKF 81297) enhanced extinction of both cued and contextual fear. These effects also occurred in the extinction of cocaine-induced conditioned place preference, suggesting that the observed effects on extinction were not specific to a particular type of procedure (aversive or appetitive). A cAMP/PKA biased D1 agonist (SKF 83959) did not affect fear extinction, whereas a broadly efficacious D1 agonist (SKF 83822) promoted fear extinction. Together, these findings show that dopamine D1/5 receptor activation is a target for the enhancement of fear or reward extinction.

  19. Pavlovian extinction, phobias, and the limits of the cognitive paradigm.

    Science.gov (United States)

    Furedy, J J; Riley, D M; Fredrikson, M

    1983-01-01

    The slow or total lack of decrease in some autonomic responses during extinction in aversive conditioning and concomitant verbalization of fear have remained a problem for learning theories and psychophysiology. Removal of the aversive stimulus should result in a rapid decrement in responding, as it does in cognitive and somatic systems. In laboratory analogues of phobia and clinical neurosis, however, such decreases do not occur in some autonomic responses and reported fear. In this article three areas of research are presented in which dissociations occur between cognitive and autonomic responses: 1) relational learning, 2) phobia, and 3) incubation. The data indicate that there are some important distinctions to be made concerning the properties of different psychological and physiological systems. These distinctions pertain to the differences between cognitive and noncognitive systems, between the two branches of the ANS, and between acquisition and extinction processes. These distinctions lead to a number of hypotheses concerning dissociations between response systems and have important implications for the understanding and treatment of neurosis.

  20. Separation of time-based and trial-based accounts of the partial reinforcement extinction effect.

    Science.gov (United States)

    Bouton, Mark E; Woods, Amanda M; Todd, Travis P

    2014-01-01

    Two appetitive conditioning experiments with rats examined time-based and trial-based accounts of the partial reinforcement extinction effect (PREE). In the PREE, the loss of responding that occurs in extinction is slower when the conditioned stimulus (CS) has been paired with a reinforcer on some of its presentations (partially reinforced) instead of every presentation (continuously reinforced). According to a time-based or "time-accumulation" view (e.g., Gallistel and Gibbon, 2000), the PREE occurs because the organism has learned in partial reinforcement to expect the reinforcer after a larger amount of time has accumulated in the CS over trials. In contrast, according to a trial-based view (e.g., Capaldi, 1967), the PREE occurs because the organism has learned in partial reinforcement to expect the reinforcer after a larger number of CS presentations. Experiment 1 used a procedure that equated partially and continuously reinforced groups on their expected times to reinforcement during conditioning. A PREE was still observed. Experiment 2 then used an extinction procedure that allowed time in the CS and the number of trials to accumulate differentially through extinction. The PREE was still evident when responding was examined as a function of expected time units to the reinforcer, but was eliminated when responding was examined as a function of expected trial units to the reinforcer. There was no evidence that the animal responded according to the ratio of time accumulated during the CS in extinction over the time in the CS expected before the reinforcer. The results thus favor a trial-based account over a time-based account of extinction and the PREE. This article is part of a Special Issue entitled: Associative and Temporal Learning.

  1. Biogeographic and bathymetric determinants of brachiopod extinction and survival during the Late Ordovician mass extinction

    DEFF Research Database (Denmark)

    Finnegan, Seth; Mac Ørum Rasmussen, Christian; Harper, David A. T.

    2016-01-01

    The Late Ordovician mass extinction (LOME) coincided with dramatic climate changes, but there are numerous ways in which these changes could have driven marine extinctions. We use a palaeobiogeographic database of rhynchonelliform brachiopods to examine the selectivity of Late Ordovician......–Early Silurian genus extinctions and evaluate which extinction drivers are best supported by the data. The first (latest Katian) pulse of the LOME preferentially affected genera restricted to deeper waters or to relatively narrow (less than 35°) palaeolatitudinal ranges. This pattern is only observed...... in the latest Katian, suggesting that it reflects drivers unique to this interval. Extinction of exclusively deeper-water genera implies that changes in water mass properties such as dissolved oxygen content played an important role. Extinction of genera with narrow latitudinal ranges suggests that interactions...

  2. Three Color Particle Optical Extinction Monitor Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose to design, build and test a multi-color (red, green, blue) particle optical extinction monitor suitable for use in either land or airborne applications....

  3. Calibrating the end-Permian mass extinction.

    Science.gov (United States)

    Shen, Shu-zhong; Crowley, James L; Wang, Yue; Bowring, Samuel A; Erwin, Douglas H; Sadler, Peter M; Cao, Chang-qun; Rothman, Daniel H; Henderson, Charles M; Ramezani, Jahandar; Zhang, Hua; Shen, Yanan; Wang, Xiang-dong; Wang, Wei; Mu, Lin; Li, Wen-zhong; Tang, Yue-gang; Liu, Xiao-lei; Liu, Lu-jun; Zeng, Yong; Jiang, Yao-fa; Jin, Yu-gan

    2011-12-09

    The end-Permian mass extinction was the most severe biodiversity crisis in Earth history. To better constrain the timing, and ultimately the causes of this event, we collected a suite of geochronologic, isotopic, and biostratigraphic data on several well-preserved sedimentary sections in South China. High-precision U-Pb dating reveals that the extinction peak occurred just before 252.28 ± 0.08 million years ago, after a decline of 2 per mil (‰) in δ(13)C over 90,000 years, and coincided with a δ(13)C excursion of -5‰ that is estimated to have lasted ≤20,000 years. The extinction interval was less than 200,000 years and synchronous in marine and terrestrial realms; associated charcoal-rich and soot-bearing layers indicate widespread wildfires on land. A massive release of thermogenic carbon dioxide and/or methane may have caused the catastrophic extinction.

  4. Possible involvement of serotonin in extinction.

    Science.gov (United States)

    Beninger, R J; Phillips, A G

    1979-01-01

    In Experiment 1, rats were trained to leverpress for continuous reinforcement with food; half were then intubated with the serotonin synthesis inhibitor parachlorophenylalanine (PCPA: 400 mg/kg) and half with water. In extinction the PCPA-treated rats responded at a higher rate. In Experiment 2, rats were trained on a random interval schedule and then assigned to two groups, treated as in Experiment 1, and tested in extinction. There was no significant difference in the resistance to extinction of the two groups. In Experiment 3, the responding of rats trained in a punished stepdown response paradigm and then given an intragastric injection of PCPA took longer to recover than the responding of water-injected controls. These observations suggest that serotonergic neurons might play a role in extinction processes.

  5. Extinction in the Lotka-Volterra model.

    Science.gov (United States)

    Parker, Matthew; Kamenev, Alex

    2009-08-01

    Birth-death processes often exhibit an oscillatory behavior. We investigate a particular case where the oscillation cycles are marginally stable on the mean-field level. An iconic example of such a system is the Lotka-Volterra model of predator-prey interaction. Fluctuation effects due to discreteness of the populations destroy the mean-field stability and eventually drive the system toward extinction of one or both species. We show that the corresponding extinction time scales as a certain power-law of the population sizes. This behavior should be contrasted with the extinction of models stable in the mean-field approximation. In the latter case the extinction time scales exponentially with size.

  6. Periodicity of extinctions in the geologic past.

    Science.gov (United States)

    Raup, D M; Sepkoski, J J

    1984-02-01

    The temporal distribution of the major extinctions over the past 250 million years has been investigated statistically using various forms of time series analysis. The analyzed record is based on variation in extinction intensity for fossil families of marine vertebrates, invertebrates, and protozoans and contains 12 extinction events. The 12 events show a statistically significant periodicity (P less than 0.01) with a mean interval between events of 26 million years. Two of the events coincide with extinctions that have been previously linked to meteorite impacts (terminal Cretaceous and Late Eocene). Although the causes of the periodicity are unknown, it is possible that they are related to extraterrestrial forces (solar, solar system, or galactic).

  7. Epidemic extinction and control in heterogeneous networks

    CERN Document Server

    Hindes, Jason

    2016-01-01

    We consider epidemic extinction in finite networks with broad variation in local connectivity. Generalizing the theory of large fluctuations to random networks with a given degree distribution, we are able to predict the most probable, or optimal, paths to extinction in various configurations, including truncated power-laws. We find that paths for heterogeneous networks follow a limiting form in which infection first decreases in low-degree nodes, which triggers a rapid extinction in high- degree nodes, and finishes with a residual low-degree extinction. The usefulness of the approach is further demonstrated through optimal control strategies that leverage finite-size fluctuations. Interestingly, we find that the optimal control is a mix of treating both high and low-degree nodes based on large-fluctuation theoretical predictions.

  8. Protostars at Low Extinction in Orion A

    CERN Document Server

    Lewis, John Arban

    2016-01-01

    In the list of young stellar objects compiled by Megeath et al. (2012) for the Orion A molecular cloud, only 44 out of 1208 sources found projected onto low extinction (Ak<0.8 mag) gas are identified as protostars. These objects are puzzling because protostars are not typically expected to be associated with extended low extinction material. Here, we use high resolution extinction maps generated from Herschel data, optical/infrared and Spitzer Space Telescope photometry and spectroscopy of the low extinction protostellar candidate sources to determine if they are likely true protostellar sources or contaminants. Out of 44 candidate objects, we determine that 10 sources are likely protostars, with the rest being more evolved young stellar objects (18), galaxies (4), false detections of nebulosity and cloud edges (9), or real sources for which more data are required to ascertain their nature (3). We find none of the confirmed protostars to be associated with recognizable dense cores and we briefly discuss po...

  9. Biomarker Records Associated with Mass Extinction Events

    Science.gov (United States)

    Whiteside, Jessica H.; Grice, Kliti

    2016-06-01

    The history of life on Earth is punctuated by a series of mass extinction episodes that vary widely in their magnitude, duration, and cause. Biomarkers are a powerful tool for the reconstruction of historical environmental conditions and can therefore provide insights into the cause and responses to ancient extinction events. In examining the five largest mass extinctions in the geological record, investigators have used biomarkers to elucidate key processes such as eutrophy, euxinia, ocean acidification, changes in hydrological balance, and changes in atmospheric CO2. By using these molecular fossils to understand how Earth and its ecosystems have responded to unusual environmental activity during these extinctions, models can be made to predict how Earth will respond to future changes in its climate.

  10. Extinction in the Galaxy from surface brightnesses of ESO-LV galaxies: testing 'standard' extinction maps

    OpenAIRE

    Choloniewski, Jacek; Valentijn, Edwin A.

    2003-01-01

    The relative extinction in the Galaxy computed with our new method (Choloniewski and Valentijn 2003, CV) is compared with three patterns: Schlegel, Finkbeiner and Davis (1998, SFD), Burstein and Heiles (1978, BH) and the cosecans law. It is shown that extinction of SFD is more reliable then that of BH since it stronger correlates with our new extinction. The smallest correlation coeffcient have been obtained for the cosecans law. Linear regression analysis show that SFD overestimate the extin...

  11. An Analysis of the Shapes of Ultraviolet Extinction Curves. IV. Extinction without Standards

    OpenAIRE

    Fitzpatrick, Edward L.; Massa, Derck

    2005-01-01

    We present a new method for deriving UV-through-IR extinction curves, based on the use of stellar atmosphere models to provide estimates of the intrinsic (i.e., unreddened) stellar spectral energy distributions (SEDs), rather than unreddened (or lightly reddened) standard stars. We show that this ``extinction-without-standards'' technique greatly increases the accuracy of the derived extinction curves and allows realistic estimations of the uncertainties. An additional benefit of the techniqu...

  12. Neural Changes Developed during the Extinction of Cocaine Self-Administration Behavior

    Directory of Open Access Journals (Sweden)

    Nuria del Olmo

    2011-10-01

    Full Text Available The high rate of recidivism in cocaine addiction after prolonged periods of abstinence poses a significant problem for the effective treatment of this condition. Moreover, the neurobiological basis of this relapse phenomenon remains poorly understood. In this review, we will discuss the evidence currently available regarding the neurobiological changes during the extinction of cocaine self-administration. Specifically, we will focus on alterations in the dopaminergic, opioidergic, glutamatergic, cholinergic, serotoninergic and CRF systems described in self-administration experiments and extinction studies after chronic cocaine administration. We will also discuss the differences related to contingent versus non-contingent cocaine administration, which highlights the importance of environmental cues on drug effects and extinction. The findings discussed in this review may aid the development of more effective therapeutic approaches to treat cocaine relapse.

  13. Neural Changes Developed during the Extinction of Cocaine Self-Administration Behavior

    Science.gov (United States)

    Higuera-Matas, Alejandro; Miguens, Miguel; del Olmo, Nuria; García-Lecumberri, Carmen; Ambrosio, Emilio

    2011-01-01

    The high rate of recidivism in cocaine addiction after prolonged periods of abstinence poses a significant problem for the effective treatment of this condition. Moreover, the neurobiological basis of this relapse phenomenon remains poorly understood. In this review, we will discuss the evidence currently available regarding the neurobiological changes during the extinction of cocaine self-administration. Specifically, we will focus on alterations in the dopaminergic, opioidergic, glutamatergic, cholinergic, serotoninergic and CRF systems described in self-administration experiments and extinction studies after chronic cocaine administration. We will also discuss the differences related to contingent versus non-contingent cocaine administration, which highlights the importance of environmental cues on drug effects and extinction. The findings discussed in this review may aid the development of more effective therapeutic approaches to treat cocaine relapse. PMID:26791639

  14. Extinction in Lotka-Volterra model

    OpenAIRE

    Parker, Matthew; Kamenev, Alex

    2009-01-01

    Competitive birth-death processes often exhibit an oscillatory behavior. We investigate a particular case where the oscillation cycles are marginally stable on the mean-field level. An iconic example of such a system is the Lotka-Volterra model of predator-prey competition. Fluctuation effects due to discreteness of the populations destroy the mean-field stability and eventually drive the system toward extinction of one or both species. We show that the corresponding extinction time scales as...

  15. Demography and the extinction of European Neanderthals

    DEFF Research Database (Denmark)

    Sørensen, Bent

    2011-01-01

    Causes previously suggested for the sudden extinction of Neanderthals (Homo neanderthalensis) in Europe, starting around 35,000 years ago, comprise food shortage, climatic effects and violence from Modern Humans. The aim here is to formulate a demographic model with reconstructed fertility and de...... Human newcomers during the last part of the period. The conclusion is that other reasons for extinction than climate or starvation must be sought....

  16. Extinction as the loss of evolutionary history

    OpenAIRE

    Erwin, Douglas H.

    2008-01-01

    Current plant and animal diversity preserves at most 1–2% of the species that have existed over the past 600 million years. But understanding the evolutionary impact of these extinctions requires a variety of metrics. The traditional measurement is loss of taxa (species or a higher category) but in the absence of phylogenetic information it is difficult to distinguish the evolutionary depth of different patterns of extinction: the same species loss can encompass very different losses of evolu...

  17. Effect of environmental variables on body size evolution of crinoids between periods of mass extinctions

    Science.gov (United States)

    Jani, T.; Heim, N. A.; Payne, J.

    2013-12-01

    Body size plays a major role in determining whether or not an organism can sustain in its local environment. The ecosystem of an animal has a major effect on the fitness of organisms, and it would be interesting to note the degree to which various environmental factors alter body size. In my project, I identify three environmental factors that seem to affect body size of crinoids, marine invertebrates from phylum Echinodermata, and explore how these variables play out in the intervals between the five mass extinctions. The particular factors I study include atmospheric CO2 concentration (proxy for temperature), O2 concentration, and sea level. Although the r and p values for all of these factors were statistically insignificant to definitively make any correlation, there was a visual correlation. For O2, I noted a generally positive correlation with body size over time. CO2 trends suggested a negative correlation until the K-T boundary, but a positive correlation afterwards. Correlation with sea level was a little more complicated: correlation was positive from the start of the Phanerozoic to the Permian extinction; it turned negative until the Cretaceous-Tertiary boundary; afterwards, it again became positive. However, for all three variables, statistical values are too low to say definitively mark any correlation. Out of all three factors, CO2 levels had the highest correlation and lowest p-values in the most time intervals: from the start of the Phanerozoic to Ordovician-Silurian Extinction, from the Late Devonian to the Permian Extinction, and from the Cretaceous-Tertiary boundary to the present. When considering first differences, CO2 levels also had the highest correlation from the Permian Extinction to Triassic-Jurassic Extinction and from the Triassic-Jurassic Extinction to Cretaceous-Tertiary Extinction. Using PaleoTS, I found that body size evolution patterns either seemed to follow either an unbiased random walk (URW) or stasis in the intervals between

  18. Evolution of the extinction curves in galaxies

    CERN Document Server

    Asano, Ryosuke S; Hirashita, Hiroyuki; Nozawa, Takaya

    2014-01-01

    We investigate the evolution of extinction curves in galaxies based on our evolution model of grain size distribution. In this model, we considered various processes: dust formation by SNe II and AGB stars, dust destruction by SN shocks in the ISM, metal accretion onto the surface of grains (referred to as grain growth), shattering and coagulation. We find that the extinction curve is flat in the earliest stage of galaxy evolution. As the galaxy is enriched with dust, shattering becomes effective to produce a large abundance of small grains ($a \\la 0.01\\;\\mu$m). Then, grain growth becomes effective at small grain radii, forming a bump at $a \\sim 10^{-3}${--}$10^{-2}\\;\\mu$m on the grain size distribution. Consequently, the extinction curve at ultraviolet (UV) wavelengths becomes steep, and a bump at $1/\\lambda \\sim 4.5\\;\\mu{\\rm m}^{-1}\\;(\\lambda: \\mbox{wavelength})$ on the extinction curve becomes prominent. Once coagulation becomes effective, the extinction curves become flatter, but the UV extinction remains...

  19. How does climate change cause extinction?

    Science.gov (United States)

    Cahill, Abigail E; Aiello-Lammens, Matthew E; Fisher-Reid, M Caitlin; Hua, Xia; Karanewsky, Caitlin J; Ryu, Hae Yeong; Sbeglia, Gena C; Spagnolo, Fabrizio; Waldron, John B; Warsi, Omar; Wiens, John J

    2013-01-07

    Anthropogenic climate change is predicted to be a major cause of species extinctions in the next 100 years. But what will actually cause these extinctions? For example, will it be limited physiological tolerance to high temperatures, changing biotic interactions or other factors? Here, we systematically review the proximate causes of climate-change related extinctions and their empirical support. We find 136 case studies of climatic impacts that are potentially relevant to this topic. However, only seven identified proximate causes of demonstrated local extinctions due to anthropogenic climate change. Among these seven studies, the proximate causes vary widely. Surprisingly, none show a straightforward relationship between local extinction and limited tolerances to high temperature. Instead, many studies implicate species interactions as an important proximate cause, especially decreases in food availability. We find very similar patterns in studies showing decreases in abundance associated with climate change, and in those studies showing impacts of climatic oscillations. Collectively, these results highlight our disturbingly limited knowledge of this crucial issue but also support the idea that changing species interactions are an important cause of documented population declines and extinctions related to climate change. Finally, we briefly outline general research strategies for identifying these proximate causes in future studies.

  20. The extinction of the West African lion: whose responsibility?

    NARCIS (Netherlands)

    A. Nollkaemper

    2014-01-01

    A recently published study showed that the lion in West Africa is now critically endangered and faces extinction. From one angle, this would be just one of the large (though unknown) number of species that has previously faced extinction or has even become extinct. But the risk of extinction of some

  1. Compound Stimulus Extinction Reduces Spontaneous Recovery in Humans

    Science.gov (United States)

    Coelho, Cesar A. O.; Dunsmoor, Joseph E.; Phelps, Elizabeth A.

    2015-01-01

    Fear-related behaviors are prone to relapse following extinction. We tested in humans a compound extinction design ("deepened extinction") shown in animal studies to reduce post-extinction fear recovery. Adult subjects underwent fear conditioning to a visual and an auditory conditioned stimulus (CSA and CSB, respectively) separately…

  2. Activation of AMPA receptor in the infralimbic cortex facilitates extinction and attenuates the heroin-seeking behavior in rats.

    Science.gov (United States)

    Chen, Weisheng; Wang, Yiqi; Sun, Anna; Zhou, Linyi; Xu, Wenjin; Zhu, Huaqiang; Zhuang, Dingding; Lai, Miaojun; Zhang, Fuqiang; Zhou, Wenhua; Liu, Huifen

    2016-01-26

    Infralimbic cortex (IL) is proposed to suppress cocaine seeking after extinction, but whether the IL regulates the extinction and reinstatement of heroin-seeking behavior is unknown. To address this issue, the male SD rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 days, then the rats underwent 7 daily 2h extinction session in the operant chamber. The activation of IL by microinjection PEPA, an allosteric AMPA receptor potentiator into IL before each of extinction session facilitated the extinction responding after heroin self-administration, but did not alter the locomotor activity in an open field testing environment. Other rats were first trained under a FR1 schedule for heroin self-administration for 14 days, followed by 14 days of extinction training, and reinstatement of heroin-seeking induced by cues was measured for 2h. Intra-IL microinjecting of PEPA at 15min prior to test inhibited the reinstatement of heroin-seeking induced by cues. Moreover, the expression of GluR1 in the IL and NAc remarkably increased after treatment with PEPA during the reinstatement. These finding suggested that activation of glutamatergic projection from IL to NAc shell may be involved in the extinction and reinstatement of heroin-seeking.

  3. Reconsolidation and extinction are dissociable and mutually exclusive processes: behavioral and molecular evidence.

    Science.gov (United States)

    Merlo, Emiliano; Milton, Amy L; Goozée, Zara Y; Theobald, David E; Everitt, Barry J

    2014-02-12

    Memory persistence is critically influenced by retrieval. In rats, a single presentation of a conditioned fear stimulus induces memory reconsolidation and fear memory persistence, while repeated fear cue presentations result in loss of fear through extinction. These two opposite behavioral outcomes are operationally linked by the number of cue presentations at memory retrieval. However, the behavioral properties and mechanistic determinants of the transition have not yet been explored; in particular, whether reconsolidation and extinction processes coexist or are mutually exclusive, depending on the exposure to non-reinforced retrieval events. We characterized both behaviorally and molecularly the transition from reconsolidation to extinction of conditioned fear and showed that an increase in calcineurin (CaN) in the basolateral amygdala (BLA) supports the shift from fear maintenance to fear inhibition. Gradually increasing the extent of retrieval induces a gradual decrease in freezing responses to the conditioned stimulus and a gradual increase in amygdala CaN level. This newly synthesized CaN is required for the extinction, but not the reconsolidation, of conditioned fear. During the transition from reconsolidation to extinction, we have revealed an insensitive state of the fear memory where NMDA-type glutamate receptor agonist and antagonist drugs are unable either to modulate CaN levels in the BLA or alter the reconsolidation or extinction processes. Together, our data indicate both that reconsolidation and extinction are mutually exclusive processes and also reveal the presence of a transitional, or "limbo," state of the original memory between these two alternative outcomes of fear memory retrieval, when neither process is engaged.

  4. Extinction rates in North American freshwater fishes, 1900-2010

    Science.gov (United States)

    Burkhead, Noel M.

    2012-01-01

    Widespread evidence shows that the modern rates of extinction in many plants and animals exceed background rates in the fossil record. In the present article, I investigate this issue with regard to North American freshwater fishes. From 1898 to 2006, 57 taxa became extinct, and three distinct populations were extirpated from the continent. Since 1989, the numbers of extinct North American fishes have increased by 25%. From the end of the nineteenth century to the present, modern extinctions varied by decade but significantly increased after 1950 (post-1950s mean = 7.5 extinct taxa per decade). In the twentieth century, freshwater fishes had the highest extinction rate worldwide among vertebrates. The modern extinction rate for North American freshwater fishes is conservatively estimated to be 877 times greater than the background extinction rate for freshwater fishes (one extinction every 3 million years). Reasonable estimates project that future increases in extinctions will range from 53 to 86 species by 2050.

  5. Implicit Learning in Transient Global Amnesia and the Role of Stress.

    Science.gov (United States)

    Nees, Frauke; Griebe, Martin; Ebert, Anne; Ruttorf, Michaela; Gerber, Benjamin; Wolf, Oliver T; Schad, Lothar R; Gass, Achim; Szabo, Kristina

    2016-01-01

    Transient global amnesia (TGA) is a disorder with reversible anterograde disturbance of explicit memory, frequently preceded by an emotionally or physically stressful event. By using magnetic resonance imaging (MRI) following an episode of TGA, small hippocampal lesions have been observed. Hence it has been postulated that the disorder is caused by the stress-related transient inhibition of memory formation in the hippocampus. In experimental studies, stress has been shown to affect both explicit and implicit learning-the latter defined as learning and memory processes that lack conscious awareness of the information acquired. To test the hypothesis that impairment of implicit learning in TGA is present and related to stress, we determined the effect of experimental exposure to stress on hippocampal activation patterns during an implicit learning paradigm in patients who suffered a recent TGA and healthy matched control subjects. We used a hippocampus-dependent aversive learning procedure (context conditioning with the phases habituation, acquisition, and extinction) during functional MRI following experimental stress exposure (socially evaluated cold pressor test). After a control procedure, controls showed successful learning during the acquisition phase, indicated by increased valence, arousal and contingency ratings to the paired (CON+) vs. the non-paired (CON-) conditioned stimulus, and successful extinction of the conditioned responses. Following stress, acquisition was still successful, however extinction was impaired with persistently increased contingency ratings. In contrast, TGA patients showed impairment of conditioned responses and insufficient extinction after the control procedure, indicated by a lack of significant differences between CON+ and CON- for valence and arousal ratings after the acquisition phase and by significantly increased contingency ratings after the extinction. After stress, aversive learning was not successful with non

  6. Implicit learning in transient global amnesia and the role of stress

    Directory of Open Access Journals (Sweden)

    Frauke Nees

    2016-11-01

    Full Text Available Transient global amnesia (TGA is a disorder with reversible anterograde disturbance of explicit memory, frequently preceded by an emotionally or physically stressful event. By using magnetic resonance imaging (MRI following an episode of TGA, small hippocampal lesions have been observed. Hence it has been postulated that the disorder is caused by the stress-related transient inhibition of memory formation in the hippocampus. In experimental studies, stress has been shown to affect both explicit and implicit learning – the latter defined as learning and memory processes that lack conscious awareness of the information acquired. To test the hypothesis that impairment of implicit learning in TGA is present and related to stress, we determined the effect of experimental exposure to stress on hippocampal activation patterns during an implicit learning paradigm in patients who suffered a recent TGA and healthy matched control subjects. We used a hippocampus-dependent aversive learning procedure (context conditioning with the phases habituation, acquisition, and extinction during functional MRI following experimental stress exposure (socially evaluated cold pressor test. After a control procedure, controls showed successful learning during the acquisition phase, indicated by increased valence, arousal and contingency ratings to the paired (CON+ versus the non-paired (CON- conditioned stimulus, and successful extinction of the conditioned responses. Following stress, acquisition was still successful, however extinction was impaired with persistently increased contingency ratings. In contrast, TGA patients showed impairment of conditioned responses and insufficient extinction after the control procedure, indicated by a lack of significant differences between CON+ and CON- for valence and arousal ratings after the acquisition phase and by significantly increased contingency ratings after the extinction. After stress, aversive learning was not successful

  7. Local extinction of a coral reef fish explained by inflexible prey choice

    Science.gov (United States)

    Brooker, R. M.; Munday, P. L.; Brandl, S. J.; Jones, G. P.

    2014-12-01

    While global extinctions of marine species are infrequent, local extinctions are becoming common. However, the role of habitat degradation and resource specialisation in explaining local extinction is unknown. On coral reefs, coral bleaching is an increasingly frequent cause of coral mortality that can result in dramatic changes to coral community composition. Coral-associated fishes are often specialised on a limited suite of coral species and are therefore sensitive to these changes. This study documents the local extinction of a corallivorous reef fish, Oxymonacanthus longirostris, following a mass bleaching event that altered the species composition of associated coral communities. Local extinction only occurred on reefs that also completely lost a key prey species, Acropora millepora, even though coral cover remained high. In an experimental test, fish continued to select bleached A. millepora over the healthy, but less-preferred prey species that resisted bleaching. These results suggest that behavioural inflexibility may limit the ability of specialists to cope with even subtle changes to resource availability.

  8. The contingent negative variation (CNV) to fear-related stimuli in acquisition and extinction.

    Science.gov (United States)

    Lumsden, J; Howard, R C; Fenton, G W

    1986-03-01

    Contingent Negative Variation (CNV) in anticipation of phobic and neutral slide material was recorded in Acquisition of a learned association between tone pitch and slide type, and in Extinction (following removal of slide presentation). In phobic volunteers, no clear CNV differentiation between 'phobic' and control condition was apparent in either Acquisition or Extinction. For Control subjects, a different pattern entirely has been demonstrated, with anticipation of the neutral condition giving rise to a larger CNV than anticipation of the 'phobic' condition (in Acquisition). In addition, Extinction led to a reversal of this CNV amplitude relationship, with the tone previously associated with the phobic slide producing a DC-shift which was larger than that following the tone previously paired with the neutral slide. The results are compatible with a dynamic model of CNV generation according to which CNV amplitude is positively related to an expectancy for reward or non-punishment but inversely related to an expectancy for punishment or non-reward.

  9. Trophically Unique Species Are Vulnerable to Cascading Extinction

    OpenAIRE

    Petchey, Owen L.; Eklöf, Anna; Borrvall, Charlotte; Ebenman, Bo

    2008-01-01

    Understanding which species might become extinct and the consequences of such loss is critical. One consequence is a cascade of further, secondary extinctions. While a significant amount is known about the types of communities and species that suffer secondary extinctions, little is known about the consequences of secondary extinctions for biodiversity. Here we examine the effect of these secondary extinctions on trophic diversity, the range of trophic roles played by the species in a communi...

  10. Low-Cost Avoidance Behaviors Are Resistant To Fear Extinction In Humans

    Directory of Open Access Journals (Sweden)

    Bram eVervliet

    2015-12-01

    Full Text Available Elevated levels of fear and avoidance are core symptoms across the anxiety disorders. It has long been known that fear serves to motivate avoidance. Consequently, fear extinction has been the primary focus in pre-clinical anxiety research for decades, under the implicit assumption that removing the motivator of avoidance (fear would automatically mitigate the avoidance behaviors as well. Although this assumption has intuitive appeal, it has received little scientific scrutiny. The scarce evidence from animal studies is mixed, while the assumption remains untested in humans. The current study applied an avoidance conditioning protocol in humans to investigate the effects of fear extinction on the persistence of low-cost avoidance. Online danger-safety ratings and skin conductance responses documented the dynamics of conditioned fear across avoidance and extinction phases. Anxiety- and avoidance-related questionnaires explored individual differences in rates of avoidance. Participants first learned to click a button during a predictive danger signal, in order to cancel an upcoming aversive electrical shock (avoidance conditioning. Next, fear extinction was induced by presenting the signal in the absence of shocks while button-clicks were prevented (by removing the button in Experiment 1, or by instructing not to click the button in Experiment 2. Most importantly, post-extinction availaibility of the button caused a significant return of avoidant button-clicks. In addition, trait-anxiety levels correlated positively with rates of avoidance during a predictive safety signal, and with the rate of pre- to post-extinction decrease during this signal. Fear measures gradually decreased during avoidance conditioning, as participants learned that button-clicks effectively canceled the shock. Preventing button-clicks elicited a sharp increase in fear, which subsequently extinguished. Fear remained low during avoidance testing, but danger-safety ratings

  11. Low-Cost Avoidance Behaviors are Resistant to Fear Extinction in Humans.

    Science.gov (United States)

    Vervliet, Bram; Indekeu, Ellen

    2015-01-01

    Elevated levels of fear and avoidance are core symptoms across the anxiety disorders. It has long been known that fear serves to motivate avoidance. Consequently, fear extinction has been the primary focus in pre-clinical anxiety research for decades, under the implicit assumption that removing the motivator of avoidance (fear) would automatically mitigate the avoidance behaviors as well. Although this assumption has intuitive appeal, it has received little scientific scrutiny. The scarce evidence from animal studies is mixed, while the assumption remains untested in humans. The current study applied an avoidance conditioning protocol in humans to investigate the effects of fear extinction on the persistence of low-cost avoidance. Online danger-safety ratings and skin conductance responses documented the dynamics of conditioned fear across avoidance and extinction phases. Anxiety- and avoidance-related questionnaires explored individual differences in rates of avoidance. Participants first learned to click a button during a predictive danger signal, in order to cancel an upcoming aversive electrical shock (avoidance conditioning). Next, fear extinction was induced by presenting the signal in the absence of shocks while button-clicks were prevented (by removing the button in Experiment 1, or by instructing not to click the button in Experiment 2). Most importantly, post-extinction availability of the button caused a significant return of avoidant button-clicks. In addition, trait-anxiety levels correlated positively with rates of avoidance during a predictive safety signal, and with the rate of pre- to post-extinction decrease during this signal. Fear measures gradually decreased during avoidance conditioning, as participants learned that button-clicks effectively canceled the shock. Preventing button-clicks elicited a sharp increase in fear, which subsequently extinguished. Fear remained low during avoidance testing, but danger-safety ratings increased again when

  12. Pre-synaptic control of remote fear extinction in the neocortex

    Directory of Open Access Journals (Sweden)

    Gisella eVetere

    2012-06-01

    Full Text Available Consolidation of remote memory enhances immediate early genes induction (IEGs, augments the expression of the presynaptic growth associated protein 43 (GAP-43, and increases the density and size of dendritic spines in anterior cingulate (aCC and infra-limbic (ILC cortices. Remote memory extinction, however, does not uniformly alter consolidation-induced structural changes. In the aCC, the density, but not the size, of spines is reset to pseudo-conditioning levels while novel thin spines are formed in the ILC. Whether IEGs and GAP-43 also undergo region-specific changes upon remote memory extinction is undetermined. Here we confirm in the same batch of mice that c-Fos induction and GAP-43 expression are increased in both the aCC and the ILC 36 days after contextual fear conditioning. We then show that, in both regions, remote memory extinction is associated with decrease of c-Fos induction but no change in GAP-43 expression thus revealing similar, although protein-specific, pre-synaptic adaptations in aCC and ILC neurons. These observations, in addition to our previous report of region-specific post-synaptic structural changes, disclose a complex pattern of extinction-driven neocortical alterations suitable to support erasure or reinstatement of fear according to the environment demand.

  13. Elevational distribution and extinction risk in birds.

    Directory of Open Access Journals (Sweden)

    Rachel L White

    Full Text Available Mountainous regions are hotspots of terrestrial biodiversity. Unlike islands, which have been the focus of extensive research on extinction dynamics, fewer studies have examined mountain ranges even though they face increasing threats from human pressures - notably habitat conversion and climate change. Limits to the taxonomic and geographical extent and resolution of previously available information have precluded an explicit assessment of the relative role of elevational distribution in determining extinction risk. We use a new global species-level avian database to quantify the influence of elevational distribution (range, maximum and midpoint on extinction risk in birds at the global scale. We also tested this relationship within biogeographic realms, higher taxonomic levels, and across phylogenetic contrasts. Potential confounding variables (i.e. phylogenetic, distributional, morphological, life history and niche breadth were also tested and controlled for. We show that the three measures of elevational distribution are strong negative predictors of avian extinction risk, with elevational range comparable and complementary to that of geographical range size. Extinction risk was also found to be positively associated with body weight, development and adult survival, but negatively associated with reproduction and niche breadth. The robust and consistent findings from this study demonstrate the importance of elevational distribution as a key driver of variation in extinction dynamics in birds. Our results also highlight elevational distribution as a missing criterion in current schemes for quantifying extinction risk and setting species conservation priorities in birds. Further research is recommended to test for generality across non-avian taxa, which will require an advance in our knowledge of species' current elevational ranges and increased efforts to digitise and centralise such data.

  14. Effects of hippocampal state-contingent trial presentation on hippocampus-dependent nonspatial classical conditioning and extinction.

    Science.gov (United States)

    Nokia, Miriam S; Wikgren, Jan

    2014-04-23

    Hippocampal local field potentials are characterized by two mutually exclusive states: one characterized by regular θ oscillations (∼4-8 Hz) and the other by irregular sharp-wave ripples. Presenting stimuli during dominant θ oscillations leads to expedited learning, suggesting that θ indexes a state in which encoding is most effective. However, ripple-contingent training also expedites learning, suggesting that any discrete brain state, much like the external context, can affect learning. We trained adult rabbits in trace eyeblink conditioning, a hippocampus-dependent nonspatial task, followed by extinction. Trials were delivered either in the presence or absence of θ or regardless of hippocampal state. Conditioning in the absence of θ led to more animals learning, although learning was slower compared with a yoked control group. Contrary to expectations, conditioning in the presence of θ did not affect learning. However, extinction was expedited both when it was conducted contingent on θ and when it was conducted in a state contrary to that used to trigger trials during conditioning. Strong phase-locking of hippocampal θ-band responses to the conditioned stimulus early on during conditioning predicted good learning. No such connection was observed during extinction. Our results suggest that any consistent hippocampal oscillatory state can potentially be used to regulate learning. However, the effects depend on the specific state and task at hand. Finally, much like the external environment, the ongoing neural state appears to act as a context for learning and memory retrieval.

  15. Effects of activation and blockade of dopamine receptors on the extinction of a passive avoidance reaction in mice with a depressive-like state.

    Science.gov (United States)

    Dubrovina, N I; Zinov'eva, D V

    2010-01-01

    Learning and extinction of a conditioned passive avoidance reaction resulting from neuropharmacological actions on dopamine D(1) and D(2) receptors were demonstrated to be specific in intact mice and in mice with a depressive-like state. Learning was degraded only after administration of the D(2) receptor antagonist sulpiride and was independent of the initial functional state of the mice. In intact mice, activation of D(2) receptors with quinpirole led to a deficit of extinction, consisting of a reduction in the ability to acquire new inhibitory learning in conditions associated with the disappearance of the expected punishment. In mice with the "behavioral despair" reaction, characterized by delayed extinction, activation of D(1) receptors with SKF38393 normalized this process, while the D(2) agonist was ineffective. A positive effect consisting of accelerated extinction of the memory of fear of the dark ("dangerous") sector of the experimental chamber was also seen on blockade of both types of dopamine receptor.

  16. Impact of Life History on Fear Memory and Extinction

    Directory of Open Access Journals (Sweden)

    Jasmin Remmes

    2016-10-01

    Full Text Available Behavioral profiles are strongly shaped by an individual’s whole life experience. The accumulation of negative experiences over lifetime is thought to promote anxiety-like behavior in adulthood (‘allostatic load hypothesis’. In contrast, the ‘mismatch hypothesis’ of psychiatric disease suggests that high levels of anxiety-like behavior are the result of a discrepancy between early and late environment. The aim of the present study was to investigate how different life histories shape the expression of anxiety-like behavior and modulate fear memory. In addition, we aimed to clarify which of the two hypotheses can better explain the modulation of anxiety and fear. For this purpose, male mice grew up under either adverse or beneficial conditions during early phase of life. In adulthood they were further subdivided in groups that either matched or mismatched the condition experienced before, resulting in four different life histories. The main results were: (i Early life benefit followed by late life adversity caused decreased levels of anxiety-like behavior. (ii Accumulation of adversity throughout life history led to impaired fear extinction learning. Late life adversity as compared to late life benefit mainly affected extinction training, while early life adversity as compared to early life benefit interfered with extinction recall. Concerning anxiety-like behavior, the results do neither support the allostatic load nor the mismatch hypothesis, but rather indicate an anxiolytic effect of a mismatched early beneficial and later adverse life history. In contrast, fear memory was strongly affected by the accumulation of adverse experiences over the lifetime, therefore supporting allostatic load hypothesis. In summary, this study highlights that anxiety-like behavior and fear memory are differently affected by specific combinations of adverse or beneficial events experienced throughout life.

  17. Extinction of food-reinforced instrumental behavior in Japanese quail (Coturnix japonica).

    Science.gov (United States)

    Buriticá, Jonathan; Ortega, Leonardo A; Papini, Mauricio R; Gutiérrez, Germán

    2013-02-01

    Japanese quail (Coturnix japonica) were reinforced with food for traversing a runway for either 18 or 36 trials, administered at a rate of 1 trial per day. Then, all animals received 18 extinction trials. The latency to run from the start box to the goal box was the dependent variable. Extinction was significantly slower in animals that had received 50% partial reinforcement during acquisition, whether relative to a group matched in terms of acquisition trials (36 trials, twice the number of reinforced trials) or relative to a group matched in terms of reinforcements (18 trials). The latter group was also matched in terms of the temporal distribution of acquisition trials with the partial reinforcement group, being trained only on days when the partial group was scheduled to receive a reinforced trial. Thus, there was evidence of a spaced-trial partial reinforcement extinction effect. A comparison of groups receiving large versus small reward magnitudes yielded no evidence of the spaced-trial magnitude of reinforcement extinction effect, even though the large-reward group consumed approximately 3 times more food than the small-reward group. Moreover, a comparison of groups that received 36 versus 18 acquisition trials produced no evidence of the spaced-trial overtraining extinction effect, even though acquisition latencies were significantly lower for the group that received 36 acquisition trials. These results are discussed in relation to comparative research on learning phenomena involving incentive downshift manipulations.

  18. Facilitation of extinction and re-extinction of operant behavior in mice by chlordiazepoxide and D-cycloserine.

    Science.gov (United States)

    Leslie, Julian C; Norwood, Kelly

    2013-05-01

    The aim was to compare operant extinction with re-extinction following re-acquisition and to investigate neuropharmacological mechanisms through administration of drugs potentiating GABAergic or glutamatergic systems. Groups of C57Bl/6 mice were trained to lever press for food on a fixed ratio schedule, then extinguished with or without pre-session chlordiazepoxide or post-session d-cycloserine administration (15mg/kg in each case), then retrained to lever press for food, then re-extinguished with or without pre-session chlordiazepoxide or post-session d-cycloserine. Under vehicle injections, extinction and re-extinction curves were indistinguishable, but drug treatments showed that there was less resistance to extinction in the re-extinction phase. Chlordiazepoxide facilitated extinction and re-extinction, with an earlier effect during re-extinction. d-Cycloserine also facilitated extinction and re-extinction, with some evidence of an earlier effect during re-extinction. These results replicate and extend earlier findings with operant extinction, but differ from some previous reports of d-cycloserine on re-extinction of Pavlovian conditioned fear. Implications for accounts of the similarities and differences between neural mechanisms of extinction following either Pavlovian or operant conditioning, and applications of these findings, are discussed.

  19. Quantitative analysis of forest fire extinction efficiency

    Directory of Open Access Journals (Sweden)

    Miguel E. Castillo-Soto

    2015-08-01

    Full Text Available Aim of study: Evaluate the economic extinction efficiency of forest fires, based on the study of fire combat undertaken by aerial and terrestrial means. Area of study, materials and methods: Approximately 112,000 hectares in Chile. Records of 5,876 forest fires that occurred between 1998 and 2009 were analyzed. The area further provides a validation sector for results, by incorporating databases for the years 2010 and 2012. The criteria used for measuring extinction efficiency were economic value of forestry resources, Contraction Factor analysis and definition of the extinction costs function. Main results: It is possible to establish a relationship between burnt area, extinction costs and economic losses. The method proposed may be used and adapted to other fire situations, requiring unit costs for aerial and terrestrial operations, economic value of the property to be protected and speed attributes of fire spread in free advance. Research highlights: The determination of extinction efficiency in containment works of forest fires and potential projection of losses, different types of plant fuel and local conditions favoring the spread of fire broaden the admissible ranges of a, φ and Ce considerably.

  20. Mass Extinctions and Biosphere-Geosphere Stability

    Science.gov (United States)

    Rothman, Daniel; Bowring, Samuel

    2015-04-01

    Five times in the past 500 million years, mass extinctions have resulted in the loss of greater than three-fourths of living species. Each of these events is associated with significant environmental change recorded in the carbon-isotopic composition of sedimentary rocks. There are also many such environmental events in the geologic record that are not associated with mass extinctions. What makes them different? Two factors appear important: the size of the environmental perturbation, and the time scale over which it occurs. We show that the natural perturbations of Earth's carbon cycle during the past 500 million years exhibit a characteristic rate of change over two orders of magnitude in time scale. This characteristic rate is consistent with the maximum rate that limits quasistatic (i.e., near steady-state) evolution of the carbon cycle. We identify this rate with marginal stability, and show that mass extinctions occur on the fast, unstable side of the stability boundary. These results suggest that the great extinction events of the geologic past, and potentially a "sixth extinction" associated with modern environmental change, are characterized by common mechanisms of instability.

  1. Determining the extragalactic extinction law with SALT

    CERN Document Server

    Finkelman, Ido; Kniazev, Alexei Y; Buckley, David; O'Donoghue, Darragh; Hashimoto, Yas; Loaring, Nicola; Romero, Encarni; Still, Martin; Vaisanen, Petri

    2008-01-01

    We present CCD imaging observations of early-type galaxies with dark lanes obtained with the Southern African Large Telescope (SALT) during its performance-verification phase. We derive the extinction law by the extragalactic dust in the dark lanes in the spectral range 1.11mu m^{-1} < lambda^{-1} < 2.94 mu m^{-1} by fitting model galaxies to the unextinguished parts of the image, and subtracting from these the actual images. We find that the extinction curves run parallel to the Galactic extinction curve, which implies that the properties of dust in the extragalactic enviroment are similar to those of the Milky Way. The ratio of the total V band extinction to the selective extinction between the V and B bands is derived for each galaxy with an average of 2.82+-0.38, compared to a canonical value of 3.1 for the Milky Way. The similar values imply that galaxies with well-defined dark lanes have characteristic dust grain sizes similar to those of Galactic dust.

  2. Interactions of time of day and sleep with between-session habituation and extinction memory in young adult males.

    Science.gov (United States)

    Pace-Schott, Edward F; Tracy, Lauren E; Rubin, Zoe; Mollica, Adrian G; Ellenbogen, Jeffrey M; Bianchi, Matt T; Milad, Mohammed R; Pitman, Roger K; Orr, Scott P

    2014-05-01

    Within-session habituation and extinction learning co-occur as do subsequent consolidation of habituation (i.e., between-session habituation) and extinction memory. We sought to determine whether, as we predicted: (1) between-session habituation is greater across a night of sleep versus a day awake; (2) time-of-day accounts for differences; (3) between-session habituation predicts consolidation of extinction memory; (4) sleep predicts between-session habituation and/or extinction memory. Participants (N = 28) completed 4-5 sessions alternating between mornings and evenings over 3 successive days (2 nights) with session 1 in either the morning (N = 13) or evening (N = 15). Twelve participants underwent laboratory polysomnography. During 4 sessions, participants completed a loud-tone habituation protocol, while skin conductance response (SCR), blink startle electromyography (EMG), heart-rate acceleration and heart-rate deceleration (HRD) were recorded. For sessions 1 and 2, between-session habituation of EMG, SCR and HRD was greater across sleep. SCR and HRD were generally lower in the morning. Between-session habituation of SCR for sessions 1 and 2 was positively related to intervening (first night) slow wave sleep. In the evening before night 2, participants also underwent fear conditioning and extinction learning phases of a second protocol. Extinction recall was tested the following morning. Extinction recall was predicted only by between-session habituation of SCR across the same night (second night) and by intervening REM. We conclude that: (1) sleep augments between-session habituation, as does morning testing; (2) extinction recall is predicted by concurrent between-session habituation; and (3) both phenomena may be influenced by sleep.

  3. Aversive Pavlovian conditioning in childhood anxiety disorders: impaired response inhibition and resistance to extinction.

    Science.gov (United States)

    Waters, Allison M; Henry, Julie; Neumann, David L

    2009-05-01

    Learning-based models of anxiety disorders emphasize the role of aversive conditioning and retarded extinction in the etiology and maintenance of anxiety disorders. Yet few studies have examined these underlying processes in children, despite that some anxiety disorders typically onset during childhood. The authors examined the acquisition and extinction of conditioned responses in 17 anxious children and 18 nonanxious control children between 8 and 12 years old using a discriminative Pavlovian conditioning procedure. One geometric shape conditional stimulus was paired with an unpleasant loud tone unconditional stimulus (CS+) whereas another geometric shape was presented alone (CS-). In the context of similar levels of discriminative conditioning in both groups, anxious children showed larger skin conductance responses to the CS+ and the CS- during acquisition and evaluated the CS+ as more arousing than the CS- compared with control children. They also showed greater resistance to extinction in skin conductance responses but not in arousal ratings to the CS+ vs. the CS- relative to control children. Results suggest that deficits in response inhibition to safety cues and retarded extinction may underlie learning processes involved in the pathogenesis of childhood anxiety disorders.

  4. Astrophysical life extinctions what killed the dinosaurs?

    CERN Document Server

    Dar, Arnon

    1999-01-01

    Geological records indicate that the exponential diversification of marine and continental life on Earth in the past 500 My was interrupted by many life extinctions. They also indicate that the major mass extinctions were correlated in time with large meteoritic impacts, gigantic volcanic eruptions, sea regressions and drastic changes in global climate. Some of these catastrophes coincided in time. The astrophysical life extinction mechanisms which were proposed so far, in particular, meteoritic impacts, nearby supernova explosions, passage through molecular or dark matter clouds, and Galactic gamma/cosmic ray bursts cannot explain the time coincidences between these catastrophes. However, recent observations suggest that many planetary-mass objects may be present in the outer solar system between the Kuiper belt and the Oort cloud. Gravitational perturbations may occasionally bring them into the inner solar system. Their passage near Earth could have generated gigantic tidal waves, large volcanic eruptions, ...

  5. Mammal extinctions, body size, and paleotemperature

    Science.gov (United States)

    Bown, T.M.; Holroyd, P.A.; Rose, K.D.

    1994-01-01

    There is a general inverse relationship between the natural logarithm of tooth area (a body size indicator) of some fossil mammals and paleotemperature during approximately 2.9 million years of the early Eocene in the Bighorn Basin of northwest Wyoming. When mean temperatures became warmer, tooth areas tended to become smaller. During colder times, larger species predominated; these generally became larger or remained the same size. Paleotemperature trends also markedly affected patterns of local (and, perhaps, regional) extinction and immigration. New species appeared as immigrants during or near the hottest (smaller forms) and coldest (larger forms) intervals. Paleotemperature trend reversals commonly resulted in the ultimate extinction of both small forms (during cooling intervals) and larger forms (during warming intervals). These immigrations and extinctions mark faunal turnovers that were also modulated by sharp increases in sediment accumulation rate.

  6. Life extinctions by neutron star mergers

    CERN Document Server

    Dar, Arnon; Shaviv, N J; Dar, Arnon; Laor, Ari; Shaviv, Nir J.

    1997-01-01

    High energy cosmic ray jets from nearby mergers or accretion induced collapse (AIC) of neutron stars (NS) that hit the atmosphere can produce lethal fluxes of atmospheric muons at ground level, underground and underwater, destroy the ozone layer and radioactivate the environment. They could have caused most of the massive life extinctions on planet Earth in the past 600 My. Biological mutations due to ionizing radiations could have caused the fast appearance of new species after the massive extinctions. An early warning of future extinctions due to NS mergers may be obtained by identifying, mapping and timing all the nearby binary neutron stars systems. A warning of an approaching cosmic ray burst from a nearby NS merger/AIC may be provided by a very intense gamma ray burst which preceeds it.

  7. Does supplementary reinforcement of stereotypy facilitate extinction?

    Science.gov (United States)

    Dozier, Claudia L; Iwata, Brian A; Wilson, David M; Thomason-Sassi, Jessica L; Roscoe, Eileen M

    2013-01-01

    Results of several studies suggest that delivery of supplemental (social) reinforcement for stereotypy might facilitate its subsequent extinction. We examined this possibility with 9 subjects who engaged in stereotypy by including methodological refinements to ensure that (a) subjects' stereotypy was maintained in the absence of social consequences, (b) supplementary reinforcers were highly preferred and were shown to be reinforcers for some behavior, and (c) subjects were exposed to lengthy reinforcement and extinction conditions. In spite of these modifications, only 4 subjects' stereotypy increased when supplementary reinforcement was delivered contingent on stereotypy, and no subject's stereotypy decreased below initial baseline levels when social reinforcement was subsequently withheld. Decreases in stereotypy occurred with the implementation of noncontingent reinforcement. Thus, delivery of supplementary reinforcers either did not increase stereotypy or did not facilitate extinction of stereotypy maintained by automatic reinforcement. We discuss the practical and conceptual bases of these results with respect to our current understanding of function-based interventions.

  8. Extinction in four species cyclic competition

    Science.gov (United States)

    Intoy, Ben; Pleimling, Michel

    2013-08-01

    When four species compete stochastically in a cyclic way, the formation of two teams of mutually neutral partners is observed. In this paper we study through numerical simulations the extinction processes that can take place in this system both in the well mixed case as well as on different types of lattices. The different routes to extinction are revealed by the probability distribution of the domination time, i.e. the time needed for one team to fully occupy the system. If swapping is allowed between neutral partners, then the probability distribution is dominated by very long-lived states where a few very large domains persist, each domain being occupied by a mix of individuals from species that form one of the teams. Many aspects of the possible extinction scenarios are lost when only considering averaged quantities, such as for example the mean domination time.

  9. Protein synthesis is not required for acquisition, consolidation, and extinction of high foot-shock active avoidance training.

    Science.gov (United States)

    González-Salinas, Sofía; Medina, Andrea C; Marín-Vignando, Vera; Ruiz-López, Clyo X; Quirarte, Gina L; Prado-Alcalá, Roberto A

    2015-01-01

    Long-term memory of active avoidance in mice is not disturbed by administration of protein synthesis inhibitors (PSIs) when relatively high levels of training are used, whereas a detrimental effect is produced with lower levels of training. PSIs also disrupt extinction of avoidance behaviors in rodents, but it is not clear whether PSIs also affect this form of learning when the behavior to be extinguished was produced by a high level of training. Experiment 1 demonstrated that rats treated with the PSI cycloheximide (CXM) 30 min before training developed normal acquisition after training with either high or low foot-shock stimulation, but that memory consolidation was hindered only after low foot-shock training. Experiment 2 demonstrated that CXM disrupted extinction when administered before the first of a series of extinction sessions when low foot-shock intensity was used during training; in contrast, after training with a higher foot-shock, the PSI treatment only interfered transiently with extinction. These results indicate that acquisition, consolidation, and extinction of active avoidance learning produced by high aversive stimulation are not dependent on protein synthesis and that these processes are governed by mechanisms different from those underlying moderate forms of learning.

  10. Impaired contextual modulation of memories in PTSD: an fMRI and psychophysiological study of extinction retention and fear renewal.

    Science.gov (United States)

    Garfinkel, Sarah N; Abelson, James L; King, Anthony P; Sripada, Rebecca K; Wang, Xin; Gaines, Laura M; Liberzon, Israel

    2014-10-01

    Post-traumatic stress disorder (PTSD) patients display pervasive fear memories, expressed indiscriminately. Proposed mechanisms include enhanced fear learning and impaired extinction or extinction recall. Documented extinction recall deficits and failure to use safety signals could result from general failure to use contextual information, a hippocampus-dependent process. This can be probed by adding a renewal phase to standard conditioning and extinction paradigms. Human subjects with PTSD and combat controls were conditioned (skin conductance response), extinguished, and tested for extinction retention and renewal in a scanner (fMRI). Fear conditioning (light paired with shock) occurred in one context, followed by extinction in another, to create danger and safety contexts. The next day, the extinguished conditioned stimulus (CS+E) was re-presented to assess extinction recall (safety context) and fear renewal (danger context). PTSD patients showed impaired extinction recall, with increased skin conductance and heightened amygdala activity to the extinguished CS+ in the safety context. However, they also showed impaired fear renewal; in the danger context, they had less skin conductance response to CS+E and lower activity in amygdala and ventral-medial prefrontal cortex compared with combat controls. Control subjects displayed appropriate contextual modulation of memory recall, with extinction (safety) memory prevailing in the safety context, and fear memory prevailing in the danger context. PTSD patients could not use safety context to sustain suppression of extinguished fear memory, but they also less effectively used danger context to enhance fear. They did not display globally enhanced fear expression, but rather showed a globally diminished capacity to use contextual information to modulate fear expression.

  11. Learning

    Directory of Open Access Journals (Sweden)

    Mohsen Laabidi

    2014-01-01

    Full Text Available Nowadays learning technologies transformed educational systems with impressive progress of Information and Communication Technologies (ICT. Furthermore, when these technologies are available, affordable and accessible, they represent more than a transformation for people with disabilities. They represent real opportunities with access to an inclusive education and help to overcome the obstacles they met in classical educational systems. In this paper, we will cover basic concepts of e-accessibility, universal design and assistive technologies, with a special focus on accessible e-learning systems. Then, we will present recent research works conducted in our research Laboratory LaTICE toward the development of an accessible online learning environment for persons with disabilities from the design and specification step to the implementation. We will present, in particular, the accessible version “MoodleAcc+” of the well known e-learning platform Moodle as well as new elaborated generic models and a range of tools for authoring and evaluating accessible educational content.

  12. Extinction Mapping of Nearby Galaxies Using LEGUS

    Science.gov (United States)

    Kahre, Lauren; Walterbos, Rene A. M.; Calzetti, Daniela; Sabbi, Elena; Ubeda, Leonardo; LEGUS Collaboration

    2017-01-01

    Extinction by dust affects studies of star formation and stellar evolution in galaxies. There are different ways to measure the distribution of dust column densities across galaxies. Here we present work based on extinctions measured towards individual massive stars.Isochrones of massive stars lie in the same location on a color-color diagram with little dependence on metallicity and luminosity class, so the extinction can be directly derived from the observed photometry. We develop a method for generating extinction maps using photometry of massive stars from the Hubble Space Telescope for the nearly 50 galaxies observed by the Legacy Extragalactic Ultraviolet Survey (LEGUS). The derived extinction maps will allow us to correct ground-based and HST Halpha maps for extinction, and will be used to constrain changes in the dust-to-gas ratio across the galaxy sample and in different star formation, metallicity and morphological environments. Previous studies have found links between galaxy metallicity and the dust-to-gas mass ratio. Dust abundance and gas metallicity are critical constraints for chemical and galaxy evolution models. We present a study of LEGUS galaxies spanning a range of distances, metallicities, and galaxy morphologies, including metal-poor dwarfs Holmberg I and II and giant spirals NGC 6503 and NGC 628. We see clear evidence for changes in the dust-to-gas mass ratio with changing metallicity. We also examine changes in the dust-to-gas mass ratio with galactocentric radius. Ultimately, we will provide constraints on the dust-to-gas mass ratio across a wide range of galaxy environments.

  13. Abrupt climate change and extinction events

    Science.gov (United States)

    Crowley, Thomas J.

    1988-01-01

    There is a growing body of theoretical and empirical support for the concept of instabilities in the climate system, and indications that abrupt climate change may in some cases contribute to abrupt extinctions. Theoretical indications of instabilities can be found in a broad spectrum of climate models (energy balance models, a thermohaline model of deep-water circulation, atmospheric general circulation models, and coupled ocean-atmosphere models). Abrupt transitions can be of several types and affect the environment in different ways. There is increasing evidence for abrupt climate change in the geologic record and involves both interglacial-glacial scale transitions and the longer-term evolution of climate over the last 100 million years. Records from the Cenozoic clearly show that the long-term trend is characterized by numerous abrupt steps where the system appears to be rapidly moving to a new equilibrium state. The long-term trend probably is due to changes associated with plate tectonic processes, but the abrupt steps most likely reflect instabilities in the climate system as the slowly changing boundary conditions caused the climate to reach some threshold critical point. A more detailed analysis of abrupt steps comes from high-resolution studies of glacial-interglacial fluctuations in the Pleistocene. Comparison of climate transitions with the extinction record indicates that many climate and biotic transitions coincide. The Cretaceous-Tertiary extinction is not a candidate for an extinction event due to instabilities in the climate system. It is quite possible that more detailed comparisons and analysis will indicate some flaws in the climate instability-extinction hypothesis, but at present it appears to be a viable candidate as an alternate mechanism for causing abrupt environmental changes and extinctions.

  14. Extinction rate fragility in population dynamics.

    Science.gov (United States)

    Khasin, M; Dykman, M I

    2009-08-01

    Population extinction is of central interest for population dynamics. It may occur from a large rare fluctuation. We find that, in contrast to related large-fluctuation effects like noise-induced interstate switching, quite generally extinction rates in multipopulation systems display fragility, where the height of the effective barrier to be overcome in the fluctuation depends on the system parameters nonanalytically. We show that one of the best-known models of epidemiology, the susceptible-infectious-susceptible model, is fragile to total population fluctuations.

  15. Extinction space--a method for the quantification and classification of changes in morphospace across extinction boundaries.

    Science.gov (United States)

    Korn, Dieter; Hopkins, Melanie J; Walton, Sonny A

    2013-10-01

    Three main modes of extinction are responsible for reductions in morphological disparity: (1) random (caused by a nonselective extinction event); (2) marginal (a symmetric, selective extinction event trimming the margin of morphospace); and (3) lateral (an asymmetric, selective extinction event eliminating one side of the morphospace). These three types of extinction event can be distinguished from one another by comparing changes in three measures of morphospace occupation: (1) the sum of range along the main axes; (2) the sum of variance; and (3) the position of the centroid. Computer simulations of various extinction events demonstrate that the pre-extinction distribution of taxa (random or normal) in the morphospace has little influence on the quantification of disparity changes, whereas the modes of the extinction events play the major role. Together, the three disparity metrics define an "extinction-space" in which different extinction events can be directly compared with one another. Application of this method to selected extinction events (Frasnian-Famennian, Devonian-Carboniferous, and Permian-Triassic) of the Ammonoidea demonstrate the similarity of the Devonian events (selective extinctions) but the striking difference from the end-Permian event (nonselective extinction). These events differ in their mode of extinction despite decreases in taxonomic diversity of similar magnitude.

  16. Confounding environmental colour and distribution shape leads to underestimation of population extinction risk.

    Directory of Open Access Journals (Sweden)

    Mike S Fowler

    Full Text Available The colour of environmental variability influences the size of population fluctuations when filtered through density dependent dynamics, driving extinction risk through dynamical resonance. Slow fluctuations (low frequencies dominate in red environments, rapid fluctuations (high frequencies in blue environments and white environments are purely random (no frequencies dominate. Two methods are commonly employed to generate the coloured spatial and/or temporal stochastic (environmental series used in combination with population (dynamical feedback models: autoregressive [AR(1] and sinusoidal (1/f models. We show that changing environmental colour from white to red with 1/f models, and from white to red or blue with AR(1 models, generates coloured environmental series that are not normally distributed at finite time-scales, potentially confounding comparison with normally distributed white noise models. Increasing variability of sample Skewness and Kurtosis and decreasing mean Kurtosis of these series alter the frequency distribution shape of the realised values of the coloured stochastic processes. These changes in distribution shape alter patterns in the probability of single and series of extreme conditions. We show that the reduced extinction risk for undercompensating (slow growing populations in red environments previously predicted with traditional 1/f methods is an artefact of changes in the distribution shapes of the environmental series. This is demonstrated by comparison with coloured series controlled to be normally distributed using spectral mimicry. Changes in the distribution shape that arise using traditional methods lead to underestimation of extinction risk in normally distributed, red 1/f environments. AR(1 methods also underestimate extinction risks in traditionally generated red environments. This work synthesises previous results and provides further insight into the processes driving extinction risk in model populations. We

  17. Dexamethasone Treatment Leads to Enhanced Fear Extinction and Dynamic Fkbp5 Regulation in Amygdala.

    Science.gov (United States)

    Sawamura, Takehito; Klengel, Torsten; Armario, Antonio; Jovanovic, Tanja; Norrholm, Seth D; Ressler, Kerry J; Andero, Raül

    2016-02-01

    Posttraumatic stress disorder (PTSD) is both a prevalent and debilitating trauma-related disorder associated with dysregulated fear learning at the core of many of its signs and symptoms. Improvements in the currently available psychological and pharmacological treatments are needed in order to improve PTSD treatment outcomes and to prevent symptom relapse. In the present study, we used a putative animal model of PTSD that included presentation of immobilization stress (IMO) followed by fear conditioning (FC) a week later. We then investigated the acute effects of GR receptor activation on the extinction (EXT) of conditioned freezing, using dexamethasone administered systemically which is known to result in suppression of the HPA axis. In our previous work, IMO followed by tone-shock-mediated FC was associated with impaired fear EXT. In this study, we administered dexamethasone 4 h before EXT training and then examined EXT retention (RET) 24 h later to determine whether dexamethasone suppression rescued EXT deficits. Dexamethasone treatment produced dose-dependent enhancement of both EXT and RET. Dexamethasone was also associated with reduced amygdala Fkbp5 mRNA expression following EXT and after RET. Moreover, DNA methylation of the Fkbp5 gene occurred in a dose-dependent and time course-dependent manner within the amygdala. Additionally, we found dynamic changes in epigenetic regulation, including Dnmt and Tet gene pathways, as a function of both fear EXT and dexamethasone suppression of the HPA axis. Together, these data suggest that dexamethasone may serve to enhance EXT by altering Fkbp5-mediated glucocorticoid sensitivity via epigenetic regulation of Fkbp5 expression.

  18. Self-extinction through optimizing selection

    Science.gov (United States)

    Parvinen, Kalle; Dieckmann, Ulf

    2013-01-01

    Evolutionary suicide is a process in which selection drives a viable population to extinction. So far, such selection-driven self-extinction has been demonstrated in models with frequency-dependent selection. This is not surprising, since frequency-dependent selection can disconnect individual-level and population-level interests through environmental feedback. Hence it can lead to situations akin to the tragedy of the commons, with adaptations that serve the selfish interests of individuals ultimately ruining a population. For frequency-dependent selection to play such a role, it must not be optimizing. Together, all published studies of evolutionary suicide have created the impression that evolutionary suicide is not possible with optimizing selection. Here we disprove this misconception by presenting and analyzing an example in which optimizing selection causes self-extinction. We then take this line of argument one step further by showing, in a further example, that selection-driven self-extinction can occur even under frequency-independent selection. PMID:23583808

  19. Opportunities and costs for preventing vertebrate extinctions

    DEFF Research Database (Denmark)

    Conde, Dalia Amor; Colchero, Fernando; Güneralp, Burak

    2015-01-01

    [2] . However, averting human-induced species extinctions within AZE sites requires enhanced planning tools to increase the chances of success [3] . Here, we assess the potential for ensuring the long-term conservation of AZE vertebrate species (157 mammals, 165 birds, 17 reptiles and 502 amphibians...

  20. Molar extinction coefficients of some fatty acids

    DEFF Research Database (Denmark)

    Sandhu, G.K.; Singh, K.; Lark, B.S.;

    2002-01-01

    ) and stearic acid (C18H36O2), has been measured at the photon energies 81, 356, 511, 662, 1173 and 1332 keV. Experimental values for the molar extinction coefficient, the effective atomic number and the electron density have been derived and compared with theoretical calculations. There is good agreement...

  1. Attentional, Associative, and Configural Mechanisms in Extinction

    Science.gov (United States)

    Larrauri, Jose A.; Schmajuk, Nestor A.

    2008-01-01

    The participation of attentional and associative mechanisms in extinction, spontaneous recovery, external disinhibition, renewal, reinstatement, and reacquisition was evaluated through computer simulations with an extant computational model of classical conditioning (N. A. Schmajuk, Y. Lam, & J. A. Gray, 1996; N. A. Schmajuk & J. A. Larrauri,…

  2. Methylphenidate Enhances Extinction of Contextual Fear

    Science.gov (United States)

    Abraham, Antony D.; Cunningham, Christopher L.; Lattal, K. Matthew

    2012-01-01

    Methylphenidate (MPH, Ritalin) is a norepinephrine and dopamine transporter blocker that is widely used in humans for treatment of attention deficit disorder and narcolepsy. Although there is some evidence that targeted microinjections of MPH may enhance fear acquisition, little is known about the effect of MPH on fear extinction. Here, we show…

  3. Time to extinction of bird populations

    NARCIS (Netherlands)

    Sæther, B-E.; Engen, S.; Møller, A.P.; Visser, M.E.; Matthysen, E.; Fiedler, W.; Lambrechts, M.M.; Becker, P.H.; Brommer, J.E.; Dickinson, J.; du Feu, C.; Gehlbach, F.R.; Merilä, J.; Rendell, W.; Robertson, R.J.; Thomson, D.L.; Török, J.

    2005-01-01

    The risk of extinction of populations has not previously been empirically related to parameters characterizing their population dynamics. To analyze this relationship, we simulated how the distribution of population dynamical characters changed as a function of time, in both the remaining and the ex

  4. Modeling the Infrared Extinction toward the Galactic Center

    CERN Document Server

    Gao, Jian; Jiang, B W

    2013-01-01

    We model the ~1--19$\\mum$ infrared (IR) extinction curve toward the Galactic Center (GC) in terms of the standard silicate-graphite interstellar dust model. The grains are taken to have a power law size distribution with an exponential decay above some size. The best-fit model for the GC IR extinction constrains the visual extinction to be Av~38--42 mag. The limitation of the model, i.e., its difficulty in simultaneously reproducing both the steep ~1--3$\\mum$ near-IR extinction and the flat ~3--8$\\mum$ mid-IR extinction is discussed. We argue that this difficulty could be alleviated by attributing the extinction toward the GC to a combination of dust in different environments: dust in diffuse regions (characterized by small Rv and steep near-IR extinction), and dust in dense regions (characterized by large Rv and flat UV extinction).

  5. Inferring modern extinction risk from fossil occupancy trajectories

    Science.gov (United States)

    Kiessling, Wolfgang; Kocsis, Adam

    2016-04-01

    Besides providing information on ancient mass extinctions and intrinsic extinction risk, the fossil record may also provide useful data for assessing the extinction risk of extant species. Here we analyse the palaeontological trajectories of geographical occupancy in extant marine species to identify species that have been declining over geological time scales and may thus be more prone to extinction than expanding species. The slopes of these occupancy trajectories are used to categorize evolutionary extinction risk. Mapping the risk at global scale we find that low to mid latitude regions are at significantly higher risk than high latitude regions. We also find a moderate correspondence between high extinction risk on geological time scales and modern extinction risk for reef corals and propose to add fossil data to the assessment of current extinction risk, especially for the notoriously data deficient marine taxa.

  6. A REMARK ON EXTINCTION OF A CLASS OF SUPERPROCESSES

    Institute of Scientific and Technical Information of China (English)

    ZHAOXUELEI

    1996-01-01

    The extinction of a class of superprocesses associated with general branching characteristics and underlying Markov processes is investigted, The extinction is closely associated with the branching characteristics and the recurrence and transience of underlying processes.

  7. Modulation of fear extinction by stress, stress hormones and estradiol: a review

    Directory of Open Access Journals (Sweden)

    Ursula eStockhorst

    2016-01-01

    Full Text Available Fear acquisition and extinction are valid models for the etiology and treatment of anxiety, trauma- and stressor-related disorders. These disorders are assumed to involve aversive learning under acute and/or chronic stress. Importantly, fear conditioning and stress share common neuronal circuits. The stress response involves multiple changes interacting in a time-dependent manner: (a the fast first-wave stress response (with central actions of noradrenaline, dopamine, serotonin, corticotropin-releasing hormone, plus increased sympathetic tone and peripheral catecholamine release and (b the second-wave stress response (with peripheral release of glucocorticoids after activation of the hypothalamus-pituitary-adrenocortical axis. Control of fear during extinction is also sensitive to these stress-response mediators. In the present review, we will thus examine current animal and human data, addressing the role of stress and single stress-response mediators for successful acquisition, consolidation and recall of fear extinction. We report studies using pharmacological manipulations targeting a number of stress-related neurotransmitters and neuromodulators (monoamines, opioids, endocannabinoids, neuropeptide Y, oxytocin, glucocorticoids and behavioral stress induction. As anxiety, trauma- and stressor-related disorders are more common in women, recent research focuses on female sex hormones and identifies a potential role for estradiol in fear extinction. We will thus summarize animal and human data on the role of estradiol and explore possible interactions with stress or stress-response mediators in extinction. This also aims at identifying time-windows of enhanced (or reduced sensitivity for fear extinction, and thus also for successful exposure therapy.

  8. Modulation of Fear Extinction by Stress, Stress Hormones and Estradiol: A Review

    Science.gov (United States)

    Stockhorst, Ursula; Antov, Martin I.

    2016-01-01

    Fear acquisition and extinction are valid models for the etiology and treatment of anxiety, trauma- and stressor-related disorders. These disorders are assumed to involve aversive learning under acute and/or chronic stress. Importantly, fear conditioning and stress share common neuronal circuits. The stress response involves multiple changes interacting in a time-dependent manner: (a) the fast first-wave stress response [with central actions of noradrenaline, dopamine, serotonin, corticotropin-releasing hormone (CRH), plus increased sympathetic tone and peripheral catecholamine release] and (b) the second-wave stress response [with peripheral release of glucocorticoids (GCs) after activation of the hypothalamus-pituitary-adrenocortical (HPA) axis]. Control of fear during extinction is also sensitive to these stress-response mediators. In the present review, we will thus examine current animal and human data, addressing the role of stress and single stress-response mediators for successful acquisition, consolidation and recall of fear extinction. We report studies using pharmacological manipulations targeting a number of stress-related neurotransmitters and neuromodulators [monoamines, opioids, endocannabinoids (eCBs), neuropeptide Y, oxytocin, GCs] and behavioral stress induction. As anxiety, trauma- and stressor-related disorders are more common in women, recent research focuses on female sex hormones and identifies a potential role for estradiol in fear extinction. We will thus summarize animal and human data on the role of estradiol and explore possible interactions with stress or stress-response mediators in extinction. This also aims at identifying time-windows of enhanced (or reduced) sensitivity for fear extinction, and thus also for successful exposure therapy. PMID:26858616

  9. Extinction and reinstatement to cocaine-associated cues in male and female juvenile rats and the role of D1 dopamine receptor.

    Science.gov (United States)

    Brenhouse, Heather C; Thompson, Britta S; Sonntag, Kai C; Andersen, Susan L

    2015-08-01

    Extinction of behaviors in response to drug-associated cues and prevention of reinstatement are integral for addiction treatment, and can reverse or ameliorate the harmful consequences of drug use. The mechanisms controlling extinction and reinstatement involve prefrontal cortical dopamine receptors, which change in expression and activity during the juvenile and adolescent transitions until they mature in adulthood. Little is known about the role that PFC D1 dopamine receptors play in extinction of drug-paired associations early in life. We used extinction of place preferences for cocaine in juvenile male and female rats following genetic, cell-specific overexpression of D1 on glutamatergic cells in the PFC. All subjects needed to demonstrate cocaine preferences for inclusion in the extinction studies. Here, male juveniles with a preference to 10 mg/kg cocaine took longer to extinguish preferences compared to both male adults and female juveniles. Female juveniles extinguished more rapidly than male juveniles at 20 mg/kg cocaine. Overexpression of D1 in juvenile males significantly facilitated extinction relative to juvenile male controls, whereas D1 prolonged expression of extinction in adults overexpressing D1 and adolescents who naturally have elevated D1 expression. These data suggest that an immature D1 profile in juveniles prevented the learning of new associations, and D1 overexpression may provide sufficient activity to facilitate extinction learning. D1 overexpression reduced reinstatement to a priming dose of cocaine in juvenile males. Together, these data show D1 expression may re-program motivational circuitry to facilitate extinction learning during juvenility that is normally unavailable to juveniles and that sex differences exist.

  10. Dopamine and extinction: a convergence of theory with fear and reward circuitry.

    Science.gov (United States)

    Abraham, Antony D; Neve, Kim A; Lattal, K Matthew

    2014-02-01

    Research on dopamine lies at the intersection of sophisticated theoretical and neurobiological approaches to learning and memory. Dopamine has been shown to be critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine's function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in reward-related tasks. A parallel and growing literature indicates that dopamine is involved in fear conditioning and extinction. These studies are consistent with long-standing ideas about appetitive-aversive interactions in learning theory and they speak to the general nature of cellular and molecular processes that underlie behavior. We review the behavioral and neurobiological literature showing a role for dopamine in fear conditioning and extinction. At a cellular level, we review dopamine signaling and receptor pharmacology, cellular and molecular events that follow dopamine receptor activation, and brain systems in which dopamine functions. At a behavioral level, we describe theories of learning and dopamine function that could describe the fundamental rules underlying how dopamine modulates different aspects of learning and memory processes.

  11. Grey Milky Way Extinction from SDSS Stellar Photometry

    OpenAIRE

    Gorbikov, Evgeny; Brosch, Noah

    2009-01-01

    We report results concerning the distribution and properties of galactic extinction at high galactic latitudes derived from stellar statistics using the Sloan Digital Sky Survey (SDSS). We use the classical Wolf diagram method to identify regions with extinction, and derive the extinction and the extinction law of the dust using all five SDSS spectral bands. We estimate the distance to the extinguishing medium using simple assumptions about the stellar populations in the line of sight. We rep...

  12. Endangered Species and Natural Resource Exploitation: Extinction vs. Coexistence

    OpenAIRE

    Tsur, Yacov; Zemel, Amos

    1994-01-01

    The threat on the survival of animal species due to intensive use of natural resources is incorporated within resource management models, paying special attention to uncertainty regarding the conditions that lead to extinction. The manner in which the potential benefits forgone due to the species extinction (denoted extinction penalty) induce more conservative exploitation policies is studied in detail. When the extinction penalty is ignored, the optimal policy is to drive the resource stock ...

  13. Hippocampal Erk Mechanisms Linking Prediction Error to Fear Extinction: Roles of Shock Expectancy and Contextual Aversive Valence

    Science.gov (United States)

    Huh, Kyu Hwan; Guzman, Yomayra F.; Tronson, Natalie C.; Guedea, Anita L.; Gao, Can; Radulovic, Jelena

    2009-01-01

    Extinction of fear requires learning that anticipated aversive events no longer occur. Animal models reveal that sustained phosphorylation of the extracellular signal-regulated kinase (Erk) in hippocampal CA1 neurons plays an important role in this process. However, the key signals triggering and regulating the activity of Erk are not known. By…

  14. Gradual extinction prevents the return of fear: Implications for the discovery of state

    Directory of Open Access Journals (Sweden)

    Samuel Joseph Gershman

    2013-11-01

    Full Text Available Fear memories are notoriously difficult to erase, often recovering over time. The longstanding explanation for this finding is that, in extinction training, a new memory is formed that competes with the old one for expression but does not otherwise modify it. This explanation is at odds with traditional models of learning such as Rescorla-Wagner and reinforcement learning. A possible reconciliation that was recently suggested is that extinction training leads to the inference of a new state that is different from the state that was in effect in the original training. This solution, however, raises a new question: under what conditions are new states, or new memories formed? Theoretical accounts implicate persistent large prediction errors in this process. As a test of this idea, we reasoned that careful design of the reinforcement schedule during extinction training could reduce these prediction errors enough to prevent the formation of a new memory, while still decreasing reinforcement sufficiently to drive modification of the old fear memory. In two Pavlovian fear-conditioning experiments, we show that gradually reducing the frequency of aversive stimuli, rather than eliminating them abruptly, prevents the recovery of fear. This finding has important implications for theories of state discovery in reinforcement learning.

  15. Effect of reinforcement, reinforcer omission and extinction on a communicative response in domestic dogs (Canis familiaris).

    Science.gov (United States)

    Bentosela, Mariana; Barrera, Gabriela; Jakovcevic, Adriana; Elgier, Angel M; Mustaca, Alba E

    2008-07-01

    There is a controversy about the mechanisms involved in the interspecific communicative behaviour in domestic dogs. The main question is whether this behaviour is a result of instrumental learning or higher cognitive skills are required. The present investigations were undertaken to study the effect of learning processes upon the gaze towards the human's face as a communicative response. To such purpose, in Study 1, gaze response was subjected to three types of reinforcement schedules: differential reinforcement, reinforcer omission, and extinction in a situation of "asking for food". Results showed a significant increase in gaze duration in the differential reinforcement phase and a significant decrease in both the omission and extinction phases. These changes were quite rapid, since they occurred only after three training trials in each phase. Furthermore, extinction resulted in animal behaviour changes, such as an increase in the distance from the experimenter, the back position and lying behaviour. This is the first systematic evaluation of the behavioural changes caused by reward withdrawal (frustration) in dogs. In Study 2, the gaze response was studied in a situation where dogs walked along with their owners/trainers. These results show that learning plays an important role in this communicative response. The possible implications of these results for service dogs are discussed.

  16. Periaqueductal gray c-Fos expression varies relative to the method of conditioned taste aversion extinction employed.

    Science.gov (United States)

    Mickley, G Andrew; Wilson, Gina N; Remus, Jennifer L; Ramos, Linnet; Ketchesin, Kyle D; Biesan, Orion R; Luchsinger, Joseph R; Prodan, Suzanna

    2011-11-14

    A conditioned taste aversion (CTA) is acquired when an animal consumes a novel taste (CS) and then experiences the symptoms of poisoning (US). Following CTA training, animals will avoid the taste that was previously associated with malaise. This defensive reaction to a learned fear can be extinguished by repeated exposure to the CS alone (CS-only; CSO-EXT). However, following a latency period in which the CS is not presented, the CTA will spontaneously recover (SR). Through the use of an explicitly unpaired extinction procedure (EU-EXT) we have shown that we can speed up extinction and attenuate SR of the CTA. Here we compared and contrasted the ability of CSO and EU extinction procedures to affect c-Fos expression in the periaqueductal gray (PAG). Fluid-deprived Sprague-Dawley rats acquired a strong CTA [via 3 pairings of 0.3% oral saccharin (SAC; the CS) and 81mg/kg i.p. lithium chloride (LiCl; the US)] followed by extinction trials consisting of multiple exposures to either, (a) the CS every-other day (CSO-EXT), or (b) CS and US on alternate days (EU-EXT). A different group of rats did not receive multiple CS exposures and served as a "no extinction" (NE) control. Both extinction procedures resulted in ≥90% reacceptance of SAC (achieving asymptotic extinction). Some of the animals were sacrificed for c-Fos immunohistochemical analysis following asymptotic extinction. Other rats entered a 30-day latency period where they drank water only. These remaining animals were then tested for SR with a final exposure to SAC before being sacrificed for c-Fos immunohistochemistry. As reported previously, rats in the CS-only group exhibited a significant SR of the CTA. However, animals in the EU extinction group reached asymptotic extinction more rapidly than did CSO rats and they did not show SR of the CTA. As compared to rats that retained their CTA, both groups of extinguished rats showed suppression in the number of c-Fos-labeled neurons in all 4 longitudinal columns of

  17. Global distribution and drivers of language extinction risk

    DEFF Research Database (Denmark)

    Amano, Tatsuya; Sandel, Brody; Eager, Heidi;

    2014-01-01

    Many of the world's languages face serious risk of extinction. Efforts to prevent this cultural loss are severely constrained by a poor understanding of the geographical patterns and drivers of extinction risk. We quantify the global distribution of language extinction risk-represented by small...

  18. Inhibition of Estradiol Synthesis Impairs Fear Extinction in Male Rats

    Science.gov (United States)

    Graham, Bronwyn M.; Milad, Mohammed R.

    2014-01-01

    Emerging research has demonstrated that the sex hormone estradiol regulates fear extinction in female rodents and women. Estradiol may also regulate fear extinction in males, given its role in synaptic plasticity in both sexes. Here we report that inhibition of estradiol synthesis during extinction training, via the aromatase inhibitor fadrozole,…

  19. Consequences of biodiversity loss diverge from expectation due to post-extinction compensatory responses

    Science.gov (United States)

    Thomsen, Matthias S.; Garcia, Clement; Bolam, Stefan G.; Parker, Ruth; Godbold, Jasmin A.; Solan, Martin

    2017-03-01

    Consensus has been reached that global biodiversity loss impairs ecosystem functioning and the sustainability of services beneficial to humanity. However, the ecosystem consequences of extinction in natural communities are moderated by compensatory species dynamics, yet these processes are rarely accounted for in impact assessments and seldom considered in conservation programmes. Here, we use marine invertebrate communities to parameterise numerical models of sediment bioturbation – a key mediator of biogeochemical cycling – to determine whether post-extinction compensatory mechanisms alter biodiversity-ecosystem function relations following non-random extinctions. We find that compensatory dynamics lead to trajectories of sediment mixing that diverge from those without compensation, and that the form, magnitude and variance of each probabilistic distribution is highly influenced by the type of compensation and the functional composition of surviving species. Our findings indicate that the generalized biodiversity-function relation curve, as derived from multiple empirical investigations of random species loss, is unlikely to yield representative predictions for ecosystem properties in natural systems because the influence of post-extinction community dynamics are under-represented. Recognition of this problem is fundamental to management and conservation efforts, and will be necessary to ensure future plans and adaptation strategies minimize the adverse impacts of the biodiversity crisis.

  20. Consequences of biodiversity loss diverge from expectation due to post-extinction compensatory responses

    Science.gov (United States)

    Thomsen, Matthias S.; Garcia, Clement; Bolam, Stefan G.; Parker, Ruth; Godbold, Jasmin A.; Solan, Martin

    2017-01-01

    Consensus has been reached that global biodiversity loss impairs ecosystem functioning and the sustainability of services beneficial to humanity. However, the ecosystem consequences of extinction in natural communities are moderated by compensatory species dynamics, yet these processes are rarely accounted for in impact assessments and seldom considered in conservation programmes. Here, we use marine invertebrate communities to parameterise numerical models of sediment bioturbation – a key mediator of biogeochemical cycling – to determine whether post-extinction compensatory mechanisms alter biodiversity-ecosystem function relations following non-random extinctions. We find that compensatory dynamics lead to trajectories of sediment mixing that diverge from those without compensation, and that the form, magnitude and variance of each probabilistic distribution is highly influenced by the type of compensation and the functional composition of surviving species. Our findings indicate that the generalized biodiversity-function relation curve, as derived from multiple empirical investigations of random species loss, is unlikely to yield representative predictions for ecosystem properties in natural systems because the influence of post-extinction community dynamics are under-represented. Recognition of this problem is fundamental to management and conservation efforts, and will be necessary to ensure future plans and adaptation strategies minimize the adverse impacts of the biodiversity crisis. PMID:28255165

  1. Strains and stressors: an analysis of touchscreen learning in genetically diverse mouse strains.

    Science.gov (United States)

    Graybeal, Carolyn; Bachu, Munisa; Mozhui, Khyobeni; Saksida, Lisa M; Bussey, Timothy J; Sagalyn, Erica; Williams, Robert W; Holmes, Andrew

    2014-01-01

    Touchscreen-based systems are growing in popularity as a tractable, translational approach for studying learning and cognition in rodents. However, while mouse strains are well known to differ in learning across various settings, performance variation between strains in touchscreen learning has not been well described. The selection of appropriate genetic strains and backgrounds is critical to the design of touchscreen-based studies and provides a basis for elucidating genetic factors moderating behavior. Here we provide a quantitative foundation for visual discrimination and reversal learning using touchscreen assays across a total of 35 genotypes. We found significant differences in operant performance and learning, including faster reversal learning in DBA/2J compared to C57BL/6J mice. We then assessed DBA/2J and C57BL/6J for differential sensitivity to an environmental insult by testing for alterations in reversal learning following exposure to repeated swim stress. Stress facilitated reversal learning (selectively during the late stage of reversal) in C57BL/6J, but did not affect learning in DBA/2J. To dissect genetic factors underlying these differences, we phenotyped a family of 27 BXD strains generated by crossing C57BL/6J and DBA/2J. There was marked variation in discrimination, reversal and extinction learning across the BXD strains, suggesting this task may be useful for identifying underlying genetic differences. Moreover, different measures of touchscreen learning were only modestly correlated in the BXD strains, indicating that these processes are comparatively independent at both genetic and phenotypic levels. Finally, we examined the behavioral structure of learning via principal component analysis of the current data, plus an archival dataset, totaling 765 mice. This revealed 5 independent factors suggestive of "reversal learning," "motivation-related late reversal learning," "discrimination learning," "speed to respond," and "motivation during

  2. Strains and stressors: an analysis of touchscreen learning in genetically diverse mouse strains.

    Directory of Open Access Journals (Sweden)

    Carolyn Graybeal

    Full Text Available Touchscreen-based systems are growing in popularity as a tractable, translational approach for studying learning and cognition in rodents. However, while mouse strains are well known to differ in learning across various settings, performance variation between strains in touchscreen learning has not been well described. The selection of appropriate genetic strains and backgrounds is critical to the design of touchscreen-based studies and provides a basis for elucidating genetic factors moderating behavior. Here we provide a quantitative foundation for visual discrimination and reversal learning using touchscreen assays across a total of 35 genotypes. We found significant differences in operant performance and learning, including faster reversal learning in DBA/2J compared to C57BL/6J mice. We then assessed DBA/2J and C57BL/6J for differential sensitivity to an environmental insult by testing for alterations in reversal learning following exposure to repeated swim stress. Stress facilitated reversal learning (selectively during the late stage of reversal in C57BL/6J, but did not affect learning in DBA/2J. To dissect genetic factors underlying these differences, we phenotyped a family of 27 BXD strains generated by crossing C57BL/6J and DBA/2J. There was marked variation in discrimination, reversal and extinction learning across the BXD strains, suggesting this task may be useful for identifying underlying genetic differences. Moreover, different measures of touchscreen learning were only modestly correlated in the BXD strains, indicating that these processes are comparatively independent at both genetic and phenotypic levels. Finally, we examined the behavioral structure of learning via principal component analysis of the current data, plus an archival dataset, totaling 765 mice. This revealed 5 independent factors suggestive of "reversal learning," "motivation-related late reversal learning," "discrimination learning," "speed to respond," and

  3. Modern 'junk food' and minimally-processed 'natural food' cafeteria diets alter the response to sweet taste but do not impair flavor-nutrient learning in rats.

    Science.gov (United States)

    Palframan, Kristen M; Myers, Kevin P

    2016-04-01

    Animals learn to prefer and increase consumption of flavors paired with postingestive nutrient sensing. Analogous effects have been difficult to observe in human studies. One possibility is experience with the modern, processed diet impairs learning. Food processing manipulates flavor, texture, sweetness, and nutrition, obscuring ordinary correspondences between sensory cues and postingestive consequences. Over time, a diet of these processed 'junk' foods may impair flavor-nutrient learning. This 'flavor-confusion' hypothesis was tested by providing rats long-term exposure to cafeteria diets of unusual breadth (2 or 3 foods per day, 96 different foods over 3 months, plus ad libitum chow). One group was fed processed foods (PF) with added sugars/fats and manipulated flavors, to mimic the sensory-nutrient properties of the modern processed diet. Another group was fed only 'natural' foods (NF) meaning minimally-processed foods without manipulated flavors or added sugars/fats (e.g., fresh fruits, vegetables, whole grains) ostensibly preserving the ordinary correspondence between flavors and nutrition. A CON group was fed chow only. In subsequent tests of flavor-nutrient learning, PF and NF rats consistently acquired strong preferences for novel nutrient-paired flavors and PF rats exhibited enhanced learned acceptance, contradicting the 'flavor-confusion' hypothesis. An unexpected finding was PF and NF diets both caused lasting reduction in ad lib sweet solution intake. Groups did not differ in reinforcing value of sugar in a progressive ratio task. In lick microstructure analysis the NF group paradoxically showed increased sucrose palatability relative to PF and CON, suggesting the diets have different effects on sweet taste evaluation.

  4. Age differences in fear retention and extinction in male Sprague-Dawley rats: effects of ethanol challenge during conditioning.

    Science.gov (United States)

    Broadwater, Margaret; Spear, Linda P

    2013-09-01

    Pavlovian fear conditioning is an ideal model to investigate how learning and memory are influenced by alcohol use during adolescence because the neural mechanisms involved have been studied extensively. In Exp 1, adolescent and adult male Sprague-Dawley rats were non-injected or injected with saline, 1 or 1.5 g/kg ethanol intraperitoneally 10 min prior to tone or context conditioning. Twenty-four hours later, animals were tested for tone or context retention and extinction, with examination of extinction retention conducted 24h thereafter. In Exp 2, a context extinction session was inserted between the tone conditioning and the tone fear retention/extinction days to reduce pre-CS baseline freezing levels at test. Basal levels of acquisition, fear retention, extinction, and extinction retention after tone conditioning were similar between adolescent and adult rats. In contrast adolescents showed faster context extinction than adults, while again not differing from adults during context acquisition, retention or extinction retention. In terms of ethanol effects, adolescents were less sensitive to ethanol-induced context retention deficits than adults. No age differences emerged in terms of tone fear retention, with ethanol disrupting tone fear retention at both ages in Exp 1, but at neither age in Exp 2, a difference seemingly due to group differences in pre-CS freezing during tone testing in Exp 1, but not Exp 2. These results suggest that age differences in the acute effects of ethanol on cognitive function are task-specific, and provide further evidence for age differences cognitive functioning in a task thought to be hippocampally related.

  5. Facilitation of fear extinction by novelty depends on dopamine acting on D1-subtype dopamine receptors in hippocampus.

    Science.gov (United States)

    Menezes, Jefferson; Alves, Niége; Borges, Sidnei; Roehrs, Rafael; de Carvalho Myskiw, Jociane; Furini, Cristiane Regina Guerino; Izquierdo, Ivan; Mello-Carpes, Pâmela B

    2015-03-31

    Extinction is the learned inhibition of retrieval. Recently it was shown that a brief exposure to a novel environment enhances the extinction of contextual fear in rats, an effect explainable by a synaptic tagging-and-capture process. Here we examine whether this also happens with the extinction of another fear-motivated task, inhibitory avoidance (IA), and whether it depends on dopamine acting on D1 or D5 receptors. Rats were trained first in IA and then in extinction of this task. The retention of extinction was measured 24 h later. A 5-min exposure to a novel environment 30 min before extinction training enhanced its retention. Right after exposure to the novelty, animals were given bilateral intrahippocampal infusions of vehicle (VEH), of the protein synthesis inhibitor anisomycin, of the D1/D5 dopaminergic antagonist SCH23390, of the PKA inhibitor Rp-cAMP or of the PKC inhibitor Gö6976, and of the PKA stimulator Sp-cAMP or of the PKC stimulator PMA. The novelty increased hippocampal dopamine levels and facilitated the extinction, which was inhibited by intrahippocampal protein synthesis inhibitor anisomysin, D1/D5 dopaminerdic antagonist SCH23390, or PKA inhibitor Rp-cAMP and unaffected by PKC inhibitor Gö6976; additionally, the hippocampal infusion of PKA stimulator Sp-cAMP reverts the effect of D1/D5 dopaminergic antagonist SCH 23390, but the infusion of PKC stimulator PMA does not. The results attest to the generality of the novelty effect on fear extinction, suggest that it relies on synaptic tagging and capture, and show that it depends on hippocampal dopamine D1 but not D5 receptors.

  6. Suppression of activity-regulated cytoskeleton-associated gene expression in the dorsal striatum attenuates extinction of cocaine-seeking.

    Science.gov (United States)

    Hearing, Matthew C; Schwendt, Marek; McGinty, Jacqueline F

    2011-07-01

    The caudate putamen (CPu) has been implicated in habit learning and neuroadaptive changes that mediate the compulsive nature of drug-seeking following chronic cocaine self-administration. Re-exposure to an operant chamber previously associated with cocaine, but not yoked-saline, increases activity-regulated cytoskeleton-associated (Arc) gene mRNA expression within the dorsolateral (dl) CPu following prolonged abstinence. In this study, we tested the hypothesis that antisense gene knockdown of Arc within the dlCPu would alter cocaine-seeking. Initial studies showed that a single infusion of Arc antisense oligodeoxynucleotide (ODN) into the dlCPu significantly attenuated the induction of Arc mRNA and Arc protein by a single cocaine exposure (20 mg/kg i.p.) compared to scrambled-ODN-infused controls. In cocaine self-administering rats, infusion of Arc antisense ODN into the dlCPu 3 h prior to a test of context-driven drug-seeking significantly attenuated Arc protein induction, but failed to alter responding during testing, suggesting striatal Arc does not facilitate context-induced drug-seeking following prolonged abstinence. However, Arc antisense ODN infusion blunted the decrease in responding during subsequent 1-h extinction tests 24 and 48 h later. Following re-exposure to a cocaine-paired context, surface expression of the AMPA-type glutamate receptor GluR1 was significantly reduced whereas GluR2 was significantly increased in the dlCPu, independent of Arc antisense ODN infusion. Together, these findings indicate an important role for Arc in neuroadaptations within brain regions responsible for drug-seeking after abstinence and direct attention to changes occurring within striatal circuitry that are necessary to break down the habitual behaviour that leads to relapse.

  7. From Pavlov to PTSD: the extinction of conditioned fear in rodents, humans, and anxiety disorders.

    Science.gov (United States)

    VanElzakker, Michael B; Dahlgren, M Kathryn; Davis, F Caroline; Dubois, Stacey; Shin, Lisa M

    2014-09-01

    Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a neutral cue to predict a biologically relevant event: after repeated predictive pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a bell, which caused them to salivate. Like sustenance, danger is biologically relevant, and neutral cues can take on great salience when they predict a threat to survival. In anxiety disorders such as posttraumatic stress disorder (PTSD), this type of conditioned fear fails to extinguish, and reminders of traumatic events can cause pathological conditioned fear responses for decades after danger has passed. In this review, we use fear conditioning and extinction studies to draw a direct line from Pavlov to PTSD and other anxiety disorders. We explain how rodent studies have informed neuroimaging studies of healthy humans and humans with PTSD. We describe several genes that have been linked to both PTSD and fear conditioning and extinction and explain how abnormalities in fear conditioning or extinction may reflect a general biomarker of anxiety disorders. Finally, we explore drug and neuromodulation treatments that may enhance therapeutic extinction in anxiety disorders.

  8. From Pavlov to PTSD: The extinction of conditioned fear in rodents, humans, and in anxiety disorders

    Science.gov (United States)

    VanElzakker, Michael B.; Dahlgren, M. Kathryn; Davis, F. Caroline; Dubois, Stacey; Shin, Lisa M.

    2014-01-01

    Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a neutral cue to predict a biologically relevant event: after repeated predictive pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a bell, which caused them to salivate. Like sustenance, danger is biologically relevant, and neutral cues can take on great salience when they predict a threat to survival. In anxiety disorders such as posttraumatic stress disorder (PTSD), this type of conditioned fear fails to extinguish, and reminders of traumatic events can cause pathological conditioned fear responses for decades after danger has passed. In this review, we use fear conditioning and extinction studies to draw a direct line from Pavlov to PTSD and other anxiety disorders. We explain how rodent studies have informed neuroimaging studies of healthy humans and humans with PTSD. We describe several genes that have been linked to both PTSD and fear conditioning and extinction and explain how abnormalities in fear conditioning or extinction may reflect a general biomarker of anxiety disorders. Finally, we explore drug and neuromodulation treatments that may enhance therapeutic extinction in anxiety disorders. PMID:24321650

  9. Extinction arouses attention to the context in a behavioral suppression method with humans.

    Science.gov (United States)

    Nelson, James Byron; Lamoureux, Jeffrey A; León, Samuel P

    2013-01-01

    One experiment assessed predictions from the attentional theory of context processing (ATCP, J. M. Rosas, J. E. Callejas-Aguilera, M. M. Ramos-Álvarez, & M. J. F. Abad, 2006, Revision of retrieval theory of forgetting: What does make information context-specific? International Journal of Psychology & Psychological Therapy, Vol. 6, pp. 147-166) that extinction arouses attention to contextual stimuli. In a video-game method, participants learned a biconditional discrimination (RG+/BG-/RY-/BY+) either after extinction of another stimulus had occurred, or not. When contextual stimuli were relevant to solving the discrimination (i.e., all RG+/BG- trials occurred in one context and all RY-/BY+ in another), prior extinction of another stimulus facilitated the discrimination, as if extinction enhanced attention to the contexts. Results are discussed briefly in terms of ATCP and the model of N. A. Schmajuk, Y. W. Lam, & J. A. Gray (1996, Latent inhibition: A neural network approach, Journal of Experimental Psychology: Animal Behavior Processes, Vol. 22, pp. 321-349).

  10. The role of the medial prefrontal cortex in the conditioning and extinction of fear

    Directory of Open Access Journals (Sweden)

    Thomas Francis Giustino

    2015-11-01

    Full Text Available Once acquired, a fearful memory can persist for a lifetime. Although learned fear can be extinguished, extinction memories are fragile. The resilience of fear memories to extinction may contribute to the maintenance of disorders of fear and anxiety, including post-traumatic stress disorder (PTSD. As such, considerable effort has been placed on understanding the neural circuitry underlying the acquisition, expression, and extinction of emotional memories in rodent models as well as in humans. A triad of brain regions, including the prefrontal cortex, hippocampus, and amygdala, form an essential brain circuit involved in fear conditioning and extinction. Within this circuit, the prefrontal cortex is thought to exert top-down control over subcortical structures to regulate appropriate behavioral responses. Importantly, a division of labor has been proposed in which the prelimbic (PL and infralimbic (IL subdivisions of the medial prefrontal cortex (mPFC regulate the expression and suppression of fear in rodents, respectively. Here we critically review the anatomical and physiological evidence that has led to this proposed dichotomy of function within mPFC. We propose that under some conditions, the PL and IL act in concert, exhibiting similar patterns of neural activity in response to aversive conditioned stimuli and during the expression or inhibition of conditioned fear. This may stem from common synaptic inputs, parallel downstream outputs, or cortico-cortical interactions. Despite this functional covariation, these mPFC subdivisions may still be coding for largely opposing behavioral outcomes, with PL biased towards fear expression and IL towards suppression.

  11. PACAP modulates the consolidation and extinction of the contextual fear conditioning through NMDA receptors.

    Science.gov (United States)

    Schmidt, S D; Myskiw, J C; Furini, C R G; Schmidt, B E; Cavalcante, L E; Izquierdo, I

    2015-02-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) has a broad spectrum of biological functions including neurotransmitter, neurotrophic and neuroprotective. Moreover, it has been suggested that PACAP plays a role in the modulation of learning and memory as well as on the modulation of glutamate signaling. Thus, in the current study we investigated in the CA1 region of hippocampus and in the basolateral amygdala (BLA) the role of PACAP in the consolidation and extinction of contextual fear conditioning (CFC) and the interaction between PACAP and NMDA receptors. Male rats with cannulae implanted in the CA1 region of the hippocampus or in the BLA received immediately after the training or extinction training of the CFC infusions of the Vehicle, PACAP-38 (40 pg/side), PACAP 6-38 (40 pg/side) or PACAP 6-38 plus D-serine (50 μg/side). After 24h, the animals were subjected to a 3-min retention test. The results indicated that in the CA1 region of hippocampus, PACAP participates in the consolidation and extinction of the CFC, and in the BLA, PACAP participates only in the consolidation of the CFC. Additionally, the results suggest that the action of PACAP on the consolidation and extinction of the CFC is mediated by the glutamate NMDA receptors.

  12. Compound stimulus extinction reduces spontaneous recovery in humans

    Science.gov (United States)

    Coelho, Cesar A.O.; Dunsmoor, Joseph E.

    2015-01-01

    Fear-related behaviors are prone to relapse following extinction. We tested in humans a compound extinction design (“deepened extinction”) shown in animal studies to reduce post-extinction fear recovery. Adult subjects underwent fear conditioning to a visual and an auditory conditioned stimulus (CSA and CSB, respectively) separately paired with an electric shock. The target CS (CSA) was extinguished alone followed by compound presentations of the extinguished CSA and nonextinguished CSB. Recovery of conditioned skin conductance responses to CSA was reduced 24 h after compound extinction, as compared with a group who received an equal number of extinction trials to the CSA alone. PMID:26572649

  13. Mass Extinction in a Simple Mathematical Biological Model

    CERN Document Server

    Tokita, K; Tokita, Kei; Yasutomi, Ayumu

    1997-01-01

    Introducing the effect of extinction into the so-called replicator equations in mathematical biology, we construct a general model of ecosystems. The present model shows mass extinction by its own extinction dynamics when the system initially has a large number of species ( diversity). The extinction dynamics shows several significant features such as a power law in basin size distribution, induction time, etc. The present theory can be a mathematical foundation of the species-area effect in the paleontologic theory for mass extinction.

  14. Exposure to music in the perinatal period enhances learning performance and alters BDNF/TrkB signaling in mice as adults.

    Science.gov (United States)

    Chikahisa, Sachiko; Sei, Hiroyoshi; Morishima, Masaki; Sano, Atsuko; Kitaoka, Kazuyoshi; Nakaya, Yutaka; Morita, Yusuke

    2006-05-15

    Music has been suggested to have a beneficial effect on various types of performance in humans. However, the physiological and molecular mechanism of this effect remains unclear. We examined the effect of music exposure during the perinatal period on learning behavior in adult mice, and measured the levels of brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB), which play critical roles in synaptic plasticity. In addition, we measured the levels of 3-phosphoinositide-dependent protein kinase-1 (PDK1) and mitogen-activated protein kinase (MAPK), downstream targets of two main pathways in BDNF/TrkB signaling. Music-exposed mice completed a maze learning task with fewer errors than the white noise-exposed mice and had lower levels of BDNF and higher levels of TrkB and PDK1 in the cortex. MAPK levels were unchanged. Furthermore, TrkB and PDK1 protein levels in the cortex showed a significant negative correlation with the number of errors on the maze. These results suggest that perinatal exposure of mice to music has an influence on BDNF/TrkB signaling and its intracellular signaling pathway targets, including PDK1, and thus may induce improved learning and memory functions.

  15. Visuomotor links in awareness: evidence from extinction.

    Science.gov (United States)

    Ricci, Raffaella; Genero, Rosanna; Colombatti, Simona; Zampieri, Daniela; Chatterjee, Anjan

    2005-05-31

    In patients with extinction, ipsilesional stimuli may abolish awareness of contralesional stimuli. Explanations of extinction often assume a serial model of processing in which sensory competition and identification precedes the selection of responses. We tested the adequacy of this assumption by examining the effects of response variables on visual awareness in six patients using signal detection analysis. Ipsilesional stimuli modulated patients' response criteria in deciding whether a contralesional stimulus was a target, and response modality (verbal or motor) modulated patients' abilities to discriminate between contralesional targets and distractors. This pattern of input variables modulating response criteria and output variables modulating discriminability indicates the extent to which attentional and intentional systems are tightly intertwined, with bi-directional effects in producing visual awareness.

  16. The role of extraterrestrial phenomena in extinction.

    Science.gov (United States)

    Raup, D M

    1988-01-01

    In the several years since the Alvarez report of anomalously high iridium concentrations at the Cretaceous-Tertiary boundary, evidence for the involvement of meteorite impacts in biological extinction has increased dramatically. Much more research will be needed, however, before meteorite impact is established as a general causal factor in extinction. Of ever greater long-term interest is the possibility that other extraterrestrial forces have had important influences on the evolution of life. To recognize the effects of such forces, it will be necessary to coordinate the research of astronomy and paleontology so that testable predictions can be formulated. It is possible that known, systematic changes in the Solar System or Galaxy have had effects on global biology and that these effects have been preserved in the paleontological record.

  17. Disruption of Responding Maintained by Conditioned Reinforcement: Alterations in Response-Conditioned-Reinforcer Relations

    Science.gov (United States)

    Lieving, Gregory A.; Reilly, Mark P.; Lattal, Kennon A.

    2006-01-01

    An observing procedure was used to investigate the effects of alterations in response-conditioned-reinforcer relations on observing. Pigeons responded to produce schedule-correlated stimuli paired with the availability of food or extinction. The contingency between observing responses and conditioned reinforcement was altered in three experiments.…

  18. Dynamics of extinction debt across five taxonomic groups.

    Science.gov (United States)

    Halley, John M; Monokrousos, Nikolaos; Mazaris, Antonios D; Newmark, William D; Vokou, Despoina

    2016-07-25

    Species extinction following habitat loss is well documented. However, these extinctions do not happen immediately. The biodiversity surplus (extinction debt) declines with some delay through the process of relaxation. Estimating the time constants of relaxation, mainly the expected time to first extinction and the commonly used time for half the extinction debt to be paid off (half-life), is crucial for conservation purposes. Currently, there is no agreement on the rate of relaxation and the factors that it depends on. Here we find that half-life increases with area for all groups examined in a large meta-analysis of extinction data. A common pattern emerges if we use average number of individuals per species before habitat loss as an area index: for mammals, birds, reptiles and plants, the relationship has an exponent close to a half. We also find that the time to first determined extinction is short and increases slowly with area.

  19. Extinction and dust properties in a clumpy medium

    CERN Document Server

    Scicluna, P

    2015-01-01

    (abridged) The dust content of the universe is primarily explored via its interaction with stellar photons, producing interstellar extinction. However, owing to the physical extension of the observing beam, observations may detect scattered photons, resulting in a change in the observed (or effective) extinction, depending on the spatial distribution of the dust and the resolution of the instrument. We investigate the influence of clumpy dust distributions on effective extinction toward embedded sources and those in the diffuse ISM. We use Monte Carlo radiative transfer to examine effective extinction for various geometries. By varying the number, optical depth and volume-filling factor of clumps in models of spherical shells and the diffuse ISM, we explore the evolution of extinction. Depending on the number of scattering events in the beam, the extinction curve steepens in homogeneous media and flattens in clumpy media. As a result, clumpy dust distributions can to reproduce extinction curves with arbitrary...

  20. Effects of broken affordance on visual extinction.

    Science.gov (United States)

    Wulff, Melanie; Humphreys, Glyn W

    2015-01-01

    Previous studies have shown that visual extinction can be reduced if two objects are positioned to "afford" an action. Here we tested if this affordance effect was disrupted by "breaking" the affordance, i.e., if one of the objects actively used in the action had a broken handle. We assessed the effects of broken affordance on recovery from extinction in eight patients with right hemisphere lesions and left-sided extinction. Patients viewed object pairs that were or were not commonly used together and that were positioned for left- or right-hand actions. In the unrelated pair conditions, either two tools or two objects were presented. In line with previous research (e.g., Riddoch et al., 2006), extinction was reduced when action-related object pairs and when unrelated tool pairs were presented compared to unrelated object pairs. There was no significant difference in recovery rate between action-related (object-tool) and unrelated tool pairs. In addition, performance with action-related objects decreased when the tool appeared on the ipsilesional side compared to when it was on the contralesional side, but only when the tool handle was intact. There were minimal effects of breaking the handle of an object rather than a tool, and there was no effect of breaking the handle on either tools or objects on single item trials. The data suggest that breaking the handle of a tool lessens the degree to which it captures attention, with this attentional capture being strongest when the tool appears on the ipsilesional side. The capture of attention by the ipsilesional item then reduces the chance of detecting the contralesional stimulus. This attentional capture effect is mediated by the affordance to the intact tool.

  1. Effects of broken affordance on visual extinction

    Directory of Open Access Journals (Sweden)

    Melanie eWulff

    2015-09-01

    Full Text Available Previous studies have shown that visual extinction can be reduced if two objects are positioned to afford an action. Here we tested if this affordance effect was disrupted by breaking the affordance – if one of the objects actively used in the action had a broken handle. We assessed the effects of broken affordance on recovery from extinction in eight patients with right hemisphere lesions and left-sided extinction. Patients viewed object pairs that were or were not commonly used together and that were positioned for left- or right-hand actions. In the unrelated pair conditions, either two tools or two objects were presented. In line with previous research (e.g., Riddoch et al., 2006, extinction was reduced when action-related object pairs and when unrelated tool pairs were presented compared to unrelated object pairs. There was no significant difference in recovery rate between action-related (object-tool and unrelated tool-tool pairs. In addition, performance with action-related objects decreased when the tool appeared on the ipsilesional side compared to when it was on the contralesional side, but only when the tool handle was intact. There were minimal effects of breaking the handle of an object rather than a tool, and there was no effect of breaking the handle on either tools or objects on single item trials. The data suggest that breaking the handle of a tool lessens the degree to which it captures attention, with this attentional capture being strongest when the tool appears on the ipsilesional side. The capture of attention by the ipsilesional item then reduces the chance of detecting the contralesional stimulus. This attentional capture effect is mediated by the affordance to the intact tool.

  2. Opportunities and costs for preventing vertebrate extinctions.

    Science.gov (United States)

    Conde, Dalia A; Colchero, Fernando; Güneralp, Burak; Gusset, Markus; Skolnik, Ben; Parr, Michael; Byers, Onnie; Johnson, Kevin; Young, Glyn; Flesness, Nate; Possingham, Hugh; Fa, John E

    2015-03-16

    Despite an increase in policy and management responses to the global biodiversity crisis, implementation of the 20 Aichi Biodiversity Targets still shows insufficient progress [1]. These targets, strategic goals defined by the United Nations Convention on Biological Diversity (CBD), address major causes of biodiversity loss in part by establishing protected areas (Target 11) and preventing species extinctions (Target 12). To achieve this, increased interventions will be required for a large number of sites and species. The Alliance for Zero Extinction (AZE) [2], a consortium of conservation-oriented organisations that aims to protect Critically Endangered and Endangered species restricted to single sites, has identified 920 species of mammals, birds, amphibians, reptiles, conifers and reef-building corals in 588 'trigger' sites [3]. These are arguably the most irreplaceable category of important biodiversity conservation sites. Protected area coverage of AZE sites is a key indicator of progress towards Target 11 [1]. Moreover, effective conservation of AZE sites is essential to achieve Target 12, as the loss of any of these sites would certainly result in the global extinction of at least one species [2]. However, averting human-induced species extinctions within AZE sites requires enhanced planning tools to increase the chances of success [3]. Here, we assess the potential for ensuring the long-term conservation of AZE vertebrate species (157 mammals, 165 birds, 17 reptiles and 502 amphibians) by calculating a conservation opportunity index (COI) for each species. The COI encompasses a set of measurable indicators that quantify the possibility of achieving successful conservation of a species in its natural habitat (COIh) and by establishing insurance populations in zoos (COIc).

  3. Rewinding the process of mammalian extinction

    OpenAIRE

    Saragusty, J.; Diecke, S.; Drukker, M.; Durrant, B.; Friedrich Ben-Nun, I.; Galli, C; Goeritz, F.; Hayashi, K; Hermes, R.; Holtze, S.; Johnson, S.; Lazzari, G.; Loi, P; Loring, J. F.; Okita, K

    2016-01-01

    With only three living individuals left on this planet, the northern white rhinoceros (Ceratotherium simum cottoni) could be considered doomed for extinction. It might still be possible, however, to rescue the (sub)species by combining novel stem cell and assisted reproductive technologies. To discuss the various practical options available to us, we convened a multidisciplinary meeting under the name "Conservation by Cellular Technologies." The outcome of this meeting and the proposed road m...

  4. Clumpy cold dark matter and biological extinctions

    CERN Document Server

    Collar, J I

    1995-01-01

    Cosmological models with cosmic string and texture seeded universes predict a present abundance of very dense clumps of Cold Dark Matter particles. Their crossing through the solar system would induce a non-negligible amount of radiation damage to all living tissue; the severity of such an episode is assessed. The estimated frequency of these crossings agrees with the apparent periodicity of the paleontological record of biological extinctions. (Phys. Lett. B, in press)

  5. Modelling dust extinction in the Magellanic Clouds

    CERN Document Server

    Zonca, Alberto; Mulas, Giacomo; Aresu, Giambattista; Cecchi-Pestellini, Cesare

    2015-01-01

    We model the extinction profiles observed in the Small and Large Magellanic clouds with a synthetic population of dust grains consisting by core-mantle particles and a collection of free-flying polycyclic aromatic hydrocarbons. All different flavors of the extinction curves observed in the Magellanic Clouds can be described by the present model, that has been previously (successfully) applied to a large sample of diffuse and translucent lines of sight in the Milky Way. We find that in the Magellanic Clouds the extinction produced by classic grains is generally larger than absorption by polycyclic aromatic hydrocarbons. Within this model, the non-linear far-UV rise is accounted for by polycyclic aromatic hydrocarbons, whose presence in turn is always associated to a gap in the size distribution of classical particles. This hints either a physical connection between (e.g., a common cause for) polycyclic aromatic hydrocarbons and the absence of middle-sized dust particles, or the need for an additional component...

  6. Resurrecting extinct interactions with extant substitutes.

    Science.gov (United States)

    Griffiths, Christine J; Hansen, Dennis M; Jones, Carl G; Zuël, Nicolas; Harris, Stephen

    2011-05-10

    There is increasing evidence that restoration ecologists should be most concerned with restoring species interactions rather than species diversity per se [1]. Rewilding with taxon substitutes, the intentional introduction of exotic species to replace the ecosystem functions of recently extinct species, is one way to reverse ecosystem dysfunction following the loss of species interactions [2]. This is highly controversial [3], in part because of a lack of rigorous scientific studies [4]. Here we present the first empirical evidence of an in situ rewilding project undertaken as a hypothesis-driven ecosystem management option. On Ile aux Aigrettes, a 25-hectare island off Mauritius, the critically endangered large-fruited endemic ebony, Diospyros egrettarum (Ebenaceae), was seed-dispersal limited after the extinction of all native large-bodied frugivores, including giant tortoises. We introduced exotic Aldabra giant tortoises, Aldabrachelys gigantea, to disperse the ebony seeds. Not only did the tortoises ingest the large fruits and disperse substantial numbers of ebony seeds, but tortoise gut passage also improved seed germination, leading to the widespread, successful establishment of new ebony seedlings. Our results demonstrate that the introduction of these exotic frugivores is aiding the recovery of ebonies. We argue for more reversible rewilding experiments to investigate whether extinct species interactions can be restored.

  7. Rewinding the process of mammalian extinction.

    Science.gov (United States)

    Saragusty, Joseph; Diecke, Sebastian; Drukker, Micha; Durrant, Barbara; Friedrich Ben-Nun, Inbar; Galli, Cesare; Göritz, Frank; Hayashi, Katsuhiko; Hermes, Robert; Holtze, Susanne; Johnson, Stacey; Lazzari, Giovanna; Loi, Pasqualino; Loring, Jeanne F; Okita, Keisuke; Renfree, Marilyn B; Seet, Steven; Voracek, Thomas; Stejskal, Jan; Ryder, Oliver A; Hildebrandt, Thomas B

    2016-07-01

    With only three living individuals left on this planet, the northern white rhinoceros (Ceratotherium simum cottoni) could be considered doomed for extinction. It might still be possible, however, to rescue the (sub)species by combining novel stem cell and assisted reproductive technologies. To discuss the various practical options available to us, we convened a multidisciplinary meeting under the name "Conservation by Cellular Technologies." The outcome of this meeting and the proposed road map that, if successfully implemented, would ultimately lead to a self-sustaining population of an extremely endangered species are outlined here. The ideas discussed here, while centered on the northern white rhinoceros, are equally applicable, after proper adjustments, to other mammals on the brink of extinction. Through implementation of these ideas we hope to establish the foundation for reversal of some of the effects of what has been termed the sixth mass extinction event in the history of Earth, and the first anthropogenic one. Zoo Biol. 35:280-292, 2016. © 2016 The Authors. Zoo Biology published by Wiley Periodicals, Inc.

  8. Glucocorticoids enhance extinction-based psychotherapy.

    Science.gov (United States)

    de Quervain, Dominique J-F; Bentz, Dorothée; Michael, Tanja; Bolt, Olivia C; Wiederhold, Brenda K; Margraf, Jürgen; Wilhelm, Frank H

    2011-04-19

    Behavioral exposure therapy of anxiety disorders is believed to rely on fear extinction. Because preclinical studies have shown that glucocorticoids can promote extinction processes, we aimed at investigating whether the administration of these hormones might be useful in enhancing exposure therapy. In a randomized, double-blind, placebo-controlled study, 40 patients with specific phobia for heights were treated with three sessions of exposure therapy using virtual reality exposure to heights. Cortisol (20 mg) or placebo was administered orally 1 h before each of the treatment sessions. Subjects returned for a posttreatment assessment 3-5 d after the last treatment session and for a follow-up assessment after 1 mo. Adding cortisol to exposure therapy resulted in a significantly greater reduction in fear of heights as measured with the acrophobia questionnaire (AQ) both at posttreatment and at follow-up, compared with placebo. Furthermore, subjects receiving cortisol showed a significantly greater reduction in acute anxiety during virtual exposure to a phobic situation at posttreatment and a significantly smaller exposure-induced increase in skin conductance level at follow-up. The present findings indicate that the administration of cortisol can enhance extinction-based psychotherapy.

  9. Minimizing extinction risk through genetic rescue

    Directory of Open Access Journals (Sweden)

    Waite, T. A.

    2005-12-01

    Full Text Available According to the genetic rescue hypothesis, immigrants can improve population persistence through their genetic contribution alone. We investigate the potential for such rescue using small, inbred laboratory populations of the bean beetle (Callosobruchus maculatus. We ask how many migrants per generation (MPG are needed to minimize the genetic component of extinction risk. During Phase 1, population size was made to fluctuate between 6 and 60 (for 10 generations. During this phase, we manipulated the number of MPG, replacing 0, 1, 3, or 5 females every generation with immigrant females. During Phase 2, we simply set an upper limit on population size (.10. Compared with the 0-MPG treatment, the other treatments were equivalently effective at improving reproductive success and reducing extinction risk. A single MPG was sufficient for genetic rescue, apparently because effective migration rate was inflated dramatically during generations when population size was small. An analysis of quasi-extinction suggests that replicate populations in the 1-MPG treatment benefited from initial purging of inbreeding depression. Populations in this treatment performed so well apparently because they received the dual benefit of purging followed by genetic infusion. Our results suggest the need for further evaluation of alternative schemes for genetic rescue.

  10. Dust properties along anomalous extinction sightlines. II. Studying extinction curves with dust models

    CERN Document Server

    Mazzei, Paola

    2010-01-01

    The large majority of extinction sight lines in our Galaxy obey a simple relation depending on one parameter, the total-to-selective extinction coefficient, Rv. Different values of Rv are able to match the whole extinction curve through different environments so characterizing normal extinction curves. In this paper more than sixty curves with large ultraviolet deviations from their best-fit one parameter curve are analyzed. These curves are fitted with dust models to shed light into the properties of the grains, the processes affecting them, and their relations with the environmental characteristics. The extinction curve models are reckoned by following recent prescriptions on grain size distributions able to describe one parameter curves for Rv values from 3.1 to 5.5. Such models, here extended down to Rv=2.0, allow us to compare the resulting properties of our deviating curves with the same as normal curves in a self-consistent framework, and thus to recover the relative trends overcoming the modeling unce...

  11. Past, present and future of host–parasite co-extinctions

    Directory of Open Access Journals (Sweden)

    Giovanni Strona

    2015-12-01

    Full Text Available Human induced ecosystem alterations and climate change are expected to drive several species to extinction. In this context, the attention of public opinion, and hence conservationists' efforts, are often targeted towards species having emotional, recreational and/or economical value. This tendency may result in a high number of extinctions happening unnoticed. Among these, many could involve parasites. Several studies have highlighted various reasons why we should care about this, that go far beyond the fact that parasites are amazingly diverse. A growing corpus of evidence suggests that parasites contribute much to ecosystems both in terms of biomass and services, and the seemingly paradoxical idea that a healthy ecosystem is one rich in parasites is becoming key to the whole concept of parasite conservation. Although various articles have covered different aspects of host–parasite co-extinctions, I feel that some important conceptual issues still need to be formally addressed. In this review, I will attempt at clarifying some of them, with the aim of providing researchers with a unifying conceptual framework that could help them designing future studies. In doing this, I will try to draw a more clear distinction between the (co-evolutionary and the ecological dimensions of co-extinction studies, since the ongoing processes that are putting parasites at risk now operate at a scale that is extremely different from the one that has shaped host–parasite networks throughout million years of co-evolution. Moreover, I will emphasize how the complexity of direct and indirect effects of parasites on ecosystems makes it much challenging to identify the mechanisms possibly leading to co-extinction events, and to predict how such events will affect ecosystems in the long run.

  12. Effects of substitution on counterflow ignition and extinction of C3 and C4 alcohols

    KAUST Repository

    Alfazazi, Adamu

    2016-06-17

    Dwindling reserves and inherent uncertainty in the price of conventional fuels necessitates a search for alternative fuels. Alcohols represent a potential source of energy for the future. The structural features of an alcohol fuel have a direct impact on combustion properties. In particular, substitution in alcohols can alter the global combustion reactivity. In this study, experiments and numerical simulations were conducted to investigate the critical conditions of extinction and autoignition of n-propanol, 1-butanol, iso-propanol and iso-butanol in non-premixed diffusion flames. Experiments were carried out in the counterflow configuration, while simulations were conducted using a skeletal chemical kinetic model for the C3 and C4 alcohols. The fuel stream consists of the pre-vaporized fuel diluted with nitrogen, while the oxidizer stream is air. The experimental results show that autoignition temperatures of the tested alcohols increase in the following order: iso-propanol > iso-butanol > 1-butanol ≈ n-propanol. The simulated results for the branched alcohols agree with the experiments, while the autoignition temperature of 1-butanol is slightly higher than that of n-propanol. For extinction, the experiments show that the extinction limits of the tested fuels increase in the following order: n-propanol ≈ 1-butanol > iso-butanol > iso-propanol. The model suggests that the extinction limits of 1-butanol is slightly higher than n-propanol with extinction strain rate of iso-butanol and iso-propanol maintaining the experimentally observed trend. The transport weighted enthalpy (TWE) and radical index (Ri) concepts were utilized to rationalize the observed reactivity trends for these fuels.

  13. The path to host extinction can lead to loss of generalist parasites.

    Science.gov (United States)

    Farrell, Maxwell J; Stephens, Patrick R; Berrang-Ford, Lea; Gittleman, John L; Davies, T Jonathan

    2015-07-01

    Host extinction can alter disease transmission dynamics, influence parasite extinction and ultimately change the nature of host-parasite systems. While theory predicts that single-host parasites are among the parasite species most susceptible to extinction following declines in their hosts, documented parasite extinctions are rare. Using a comparative approach, we investigate how the richness of single-host and multi-host parasites is influenced by extinction risk among ungulate and carnivore hosts. Host-parasite associations for free-living carnivores (order Carnivora) and terrestrial ungulates (orders Perissodactyla + Cetartiodactyla minus cetaceans) were merged with host trait data and IUCN Red List status to explore the distribution of single-host and multi-host parasites among threatened and non-threatened hosts. We find that threatened ungulates harbour a higher proportion of single-host parasites compared to non-threatened ungulates, which is explained by decreases in the richness of multi-host parasites. However, among carnivores threat status is not a significant predictor of the proportion of single-host parasites, or the richness of single-host or multi-host parasites. The loss of multi-host parasites from threatened ungulates may be explained by decreased cross-species contact as hosts decline and habitats become fragmented. Among carnivores, threat status may not be important in predicting patterns of parasite specificity because host decline results in equal losses of both single-host parasites and multi-host parasites through reduction in average population density and frequency of cross-species contact. Our results contrast with current models of parasite coextinction and highlight the need for updated theories that are applicable across host groups and account for both inter- and intraspecific contact.

  14. 5-HTT deficiency affects neuroplasticity and increases stress sensitivity resulting in altered spatial learning performance in the Morris water maze but not in the Barnes maze.

    Directory of Open Access Journals (Sweden)

    Margherita M Karabeg

    Full Text Available The purpose of this study was to evaluate whether spatial hippocampus-dependent learning is affected by the serotonergic system and stress. Therefore, 5-HTT knockout (-/-, heterozygous (+/- and wildtype (+/+ mice were subjected to the Barnes maze (BM and the Morris water maze (WM, the latter being discussed as more aversive. Additionally, immediate early gene (IEG expression, hippocampal adult neurogenesis (aN, and blood plasma corticosterone were analyzed. While the performance of 5-HTT-/- mice in the BM was undistinguishable from both other genotypes, they performed worse in the WM. However, in the course of the repeated WM trials 5-HTT-/- mice advanced to wildtype level. The experience of a single trial of either the WM or the BM resulted in increased plasma corticosterone levels in all genotypes. After several trials 5-HTT-/- mice exhibited higher corticosterone concentrations compared with both other genotypes in both tests. Corticosterone levels were highest in 5-HTT-/- mice tested in the WM indicating greater aversiveness of the WM and a greater stress sensitivity of 5-HTT deficient mice. Quantitative immunohistochemistry in the hippocampus revealed increased cell counts positive for the IEG products cFos and Arc as well as for proliferation marker Ki67 and immature neuron marker NeuroD in 5-HTT-/- mice compared to 5-HTT+/+ mice, irrespective of the test. Most differences were found in the suprapyramidal blade of the dentate gyrus of the septal hippocampus. Ki67-immunohistochemistry revealed a genotype x environment interaction with 5-HTT genotype differences in naïve controls and WM experience exclusively yielding more Ki67-positive cells in 5-HTT+/+ mice. Moreover, in 5-HTT-/- mice we demonstrate that learning performance correlates with the extent of aN. Overall, higher baseline IEG expression and increased an in the hippocampus of 5-HTT-/- mice together with increased stress sensitivity may constitute the neurobiological correlate of

  15. 5-HTT deficiency affects neuroplasticity and increases stress sensitivity resulting in altered spatial learning performance in the Morris water maze but not in the Barnes maze.

    Science.gov (United States)

    Karabeg, Margherita M; Grauthoff, Sandra; Kollert, Sina Y; Weidner, Magdalena; Heiming, Rebecca S; Jansen, Friederike; Popp, Sandy; Kaiser, Sylvia; Lesch, Klaus-Peter; Sachser, Norbert; Schmitt, Angelika G; Lewejohann, Lars

    2013-01-01

    The purpose of this study was to evaluate whether spatial hippocampus-dependent learning is affected by the serotonergic system and stress. Therefore, 5-HTT knockout (-/-), heterozygous (+/-) and wildtype (+/+) mice were subjected to the Barnes maze (BM) and the Morris water maze (WM), the latter being discussed as more aversive. Additionally, immediate early gene (IEG) expression, hippocampal adult neurogenesis (aN), and blood plasma corticosterone were analyzed. While the performance of 5-HTT-/- mice in the BM was undistinguishable from both other genotypes, they performed worse in the WM. However, in the course of the repeated WM trials 5-HTT-/- mice advanced to wildtype level. The experience of a single trial of either the WM or the BM resulted in increased plasma corticosterone levels in all genotypes. After several trials 5-HTT-/- mice exhibited higher corticosterone concentrations compared with both other genotypes in both tests. Corticosterone levels were highest in 5-HTT-/- mice tested in the WM indicating greater aversiveness of the WM and a greater stress sensitivity of 5-HTT deficient mice. Quantitative immunohistochemistry in the hippocampus revealed increased cell counts positive for the IEG products cFos and Arc as well as for proliferation marker Ki67 and immature neuron marker NeuroD in 5-HTT-/- mice compared to 5-HTT+/+ mice, irrespective of the test. Most differences were found in the suprapyramidal blade of the dentate gyrus of the septal hippocampus. Ki67-immunohistochemistry revealed a genotype x environment interaction with 5-HTT genotype differences in naïve controls and WM experience exclusively yielding more Ki67-positive cells in 5-HTT+/+ mice. Moreover, in 5-HTT-/- mice we demonstrate that learning performance correlates with the extent of aN. Overall, higher baseline IEG expression and increased an in the hippocampus of 5-HTT-/- mice together with increased stress sensitivity may constitute the neurobiological correlate of raised

  16. Murine GRPR and stathmin control in opposite directions both cued fear extinction and neural activities of the amygdala and prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Guillaume Martel

    Full Text Available Extinction is an integral part of normal healthy fear responses, while it is compromised in several fear-related mental conditions in humans, such as post-traumatic stress disorder (PTSD. Although much research has recently been focused on fear extinction, its molecular and cellular underpinnings are still unclear. The development of animal models for extinction will greatly enhance our approaches to studying its neural circuits and the mechanisms involved. Here, we describe two gene-knockout mouse lines, one with impaired and another with enhanced extinction of learned fear. These mutant mice are based on fear memory-related genes, stathmin and gastrin-releasing peptide receptor (GRPR. Remarkably, both mutant lines showed changes in fear extinction to the cue but not to the context. We performed indirect imaging of neuronal activity on the second day of cued extinction, using immediate-early gene c-Fos. GRPR knockout mice extinguished slower (impaired extinction than wildtype mice, which was accompanied by an increase in c-Fos activity in the basolateral amygdala and a decrease in the prefrontal cortex. By contrast, stathmin knockout mice extinguished faster (enhanced extinction and showed a decrease in c-Fos activity in the basolateral amygdala and an increase in the prefrontal cortex. At the same time, c-Fos activity in the dentate gyrus was increased in both mutant lines. These experiments provide genetic evidence that the balance between neuronal activities of the amygdala and prefrontal cortex defines an impairment or facilitation of extinction to the cue while the hippocampus is involved in the context-specificity of extinction.

  17. Altered ERK1/2 Signaling in the Brain of Learned Helpless Rats: Relevance in Vulnerability to Developing Stress-Induced Depression

    Directory of Open Access Journals (Sweden)

    Yogesh Dwivedi

    2016-01-01

    Full Text Available Extracellular signal-regulated kinase 1/2- (ERK1/2- mediated cellular signaling plays a major role in synaptic and structural plasticity. Although ERK1/2 signaling has been shown to be involved in stress and depression, whether vulnerability to develop depression is associated with abnormalities in ERK1/2 signaling is not clearly known. The present study examined ERK1/2 signaling in frontal cortex and hippocampus of rats that showed vulnerability (learned helplessness, (LH or resiliency (non-learned helplessness, (non-LH to developing stress-induced depression. In frontal cortex and hippocampus of LH rats, we found that mRNA and protein expressions of ERK1 and ERK2 were significantly reduced, which was associated with their reduced activation and phosphorylation in cytosolic and nuclear fractions, where ERK1 and ERK2 target their substrates. In addition, ERK1/2-mediated catalytic activities and phosphorylation of downstream substrates RSK1 (cytosolic and nuclear and MSK1 (nuclear were also lower in the frontal cortex and hippocampus of LH rats without any change in their mRNA or protein expression. None of these changes were evident in non-LH rats. Our study indicates that ERK1/2 signaling is differentially regulated in LH and non-LH rats and suggests that abnormalities in ERK1/2 signaling may be crucial in the vulnerability to developing depression.

  18. Diazepam effects on aversive memory retrieval and extinction: Role of anxiety levels.

    Science.gov (United States)

    Leão, Anderson H F F; Cabral, Alícia; Izídio, Geison S; Ribeiro, Alessandra M; Silva, Regina H

    2016-02-01

    Benzodiazepines (BDZs) are anxiolytic drugs that impair memory acquisition. Previous studies using the plus-maze discriminative avoidance task (PMDAT, which assesses memory and anxiety concomitantly) indicated that the effects of BDZs on anxiety and acquisition are related to each other. The possible influence of the anxiolytic action of BDZs on their effects on memory retrieval and extinction are poorly understood. This is relevant considering the relationship between aversive memories and anxiety disorders. We designed a modified protocol of PMDAT that evaluates anxiety during retrieval and extinction of the task. Male Wistar rats were trained in the PMDAT (plus-maze with two open and two enclosed arms) using a standard or a modified protocol. In the standard protocol, the aversive stimuli were presented in one of the enclosed arms during training, and the animal had free access to the whole apparatus. In the modified protocol, the open arms were blocked with glass walls. Twenty-four hours after training, the animals subjected to each of the protocols were treated with saline or 2.0mg/kg of diazepam (DZP) 30min before the test. There was a third session in the maze (retest) 24h after the test. During the test, DZP impaired and improved retrieval in rats that had been trained in the standard and the modified protocol when compared to the respective saline-treated groups. In addition, treatment with DZP prior to the test induced anxiolysis, but only in the animals that were not pre-exposed to the open arms of the apparatus (modified protocol). In these animals, DZP impaired extinction, which was evaluated during retest session. The impairing effect of DZP on extinction seems to be related to its anxiolytic action during the test (extinction learning). Further, we suggest that aversive memory retrieval depends on both the treatment and the arousal elicited by exposure to the apparatus.

  19. Molecular mechanisms of D-cycloserine in facilitating fear extinction: insights from RNAseq.

    Science.gov (United States)

    Malan-Müller, Stefanie; Fairbairn, Lorren; Daniels, Willie M U; Dashti, Mahjoubeh Jalali Sefid; Oakeley, Edward J; Altorfer, Marc; Kidd, Martin; Seedat, Soraya; Gamieldien, Junaid; Hemmings, Sîan Megan Joanna

    2016-02-01

    D-cycloserine (DCS) has been shown to be effective in facilitating fear extinction in animal and human studies, however the precise mechanisms whereby the co-administration of DCS and behavioural fear extinction reduce fear are still unclear. This study investigated the molecular mechanisms of intrahippocampally administered D-cycloserine in facilitating fear extinction in a contextual fear conditioning animal model. Male Sprague Dawley rats (n = 120) were grouped into four experimental groups (n = 30) based on fear conditioning and intrahippocampal administration of either DCS or saline. The light/dark avoidance test was used to differentiate maladapted (MA) (anxious) from well-adapted (WA) (not anxious) subgroups. RNA extracted from the left dorsal hippocampus was used for RNA sequencing and gene expression data was compared between six fear-conditioned + saline MA (FEAR + SALINE MA) and six fear-conditioned + DCS WA (FEAR + DCS WA) animals. Of the 424 significantly downregulated and 25 significantly upregulated genes identified in the FEAR + DCS WA group compared to the FEAR + SALINE MA group, 121 downregulated and nine upregulated genes were predicted to be relevant to fear conditioning and anxiety and stress-related disorders. The majority of downregulated genes transcribed immune, proinflammatory and oxidative stress systems molecules. These molecules mediate neuroinflammation and cause neuronal damage. DCS also regulated genes involved in learning and memory processes, and genes associated with anxiety, stress-related disorders and co-occurring diseases (e.g., cardiovascular diseases, digestive system diseases and nervous system diseases). Identifying the molecular underpinnings of DCS-mediated fear extinction brings us closer to understanding the process of fear extinction.

  20. Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning.

    Science.gov (United States)

    Catlow, Briony J; Song, Shijie; Paredes, Daniel A; Kirstein, Cheryl L; Sanchez-Ramos, Juan

    2013-08-01

    Drugs that modulate serotonin (5-HT) synaptic concentrations impact neurogenesis and hippocampal (HPC)-dependent learning. The primary objective is to determine the extent to which psilocybin (PSOP) modulates neurogenesis and thereby affects acquisition and extinction of HPC-dependent trace fear conditioning. PSOP, the 5-HT2A agonist 25I-NBMeO and the 5-HT2A/C antagonist ketanserin were administered via an acute intraperitoneal injection to mice. Trace fear conditioning was measured as the amount of time spent immobile in the presence of the conditioned stimulus (CS, auditory tone), trace (silent interval) and post-trace interval over 10 trials. Extinction was determined by the number of trials required to resume mobility during CS, trace and post-trace when the shock was not delivered. Neurogenesis was determined by unbiased counts of cells in the dentate gyrus of the HPC birth-dated with BrdU co-expressing a neuronal marker. Mice treated with a range of doses of PSOP acquired a robust conditioned fear response. Mice injected with low doses of PSOP extinguished cued fear conditioning significantly more rapidly than high-dose PSOP or saline-treated mice. Injection of PSOP, 25I-NBMeO or ketanserin resulted in significant dose-dependent decreases in number of newborn neurons in hippocampus. At the low doses of PSOP that enhanced extinction, neurogenesis was not decreased, but rather tended toward an increase. Extinction of "fear conditioning" may be mediated by actions of the drugs at sites other than hippocampus such as the amygdala, which is known to mediate the perception of fear. Another caveat is that PSOP is not purely selective for 5-HT2A receptors. PSOP facilitates extinction of the classically conditioned fear response, and this, and similar agents, should be explored as potential treatments for post-traumatic stress disorder and related conditions.